Week 1 Lecture 1: Haematopoiesis Flashcards
(199 cards)
1
Q
What is the purpose of blood?
A
Transporting oxygen and blood to the lungs and tissues, forms blood clots to prevent blood loss if circulation is damaged, prevents/fights infection.
2
Q
What is the % composition of blood?
A
55% plasma, 44% red blood cells, 1% white blood cells.
3
Q
How much of plasma is made up of water?
A
90%.
4
Q
What is plasma made up of?
A
Water, electrolytes, proteins, nutrients, waste products, and hormones.
5
Q
What is haematopoiesis?
A
The production of blood cells.
6
Q
What does haematopoiesis involve?
A
The formation, development, and differentiation of blood cells from haematopoietic stem cells (HSCs).
7
Q
What is haematopoiesis important for?
A
Adequate oxygen and blood supply, immune response, and blood clotting.
8
Q
What is the main difference between serum and plasma tests?
A
Serum tests allow clotting, whereas plasma tests do not.
9
Q
What is the order of events in a serum test?
A
Blood is allowed to clot, removing the blood cells and clotting factors (e.g. fibrinogen). The resulting clot is removed via centrifugation, leaving the serum (clear, yellow liquid). Serum therefore contains the liquid form of blood without the clotting factors.
10
Q
What is serum used for?
A
Clinical chemistry tests, e.g. kidney function tests, liver function tests, lipid profiles.
11
Q
What qualities are involved in clotting screens?
A
Prothrombin time (PT), Activated Partial Thromboplastin Time (APTT), and Fibrinogen tests.
12
Q
what does prothrombin time assess?
A
the extrinsic pathway of blood clotting, which is activated by tissue damage
13
Q
what is the extrinsic pathway?
A
rapid blood clotting mechanism initiated by tissue damage outside the blood vessels
14
Q
what is the order of steps in the extrinsic pathway?
A
tissue factor (TF) is released by injured cells, which interacts with factor VII, which interacts with factor X which leads to clot formation
15
Q
how does factor X form a clot?
A
activated factor X enters the common pathway, where prothrombin is converted to thrombin, which converts fibrinogen to fibrin to form blood clots
16
Q
what is the difference between the intrinsic and extrinsic pathway?
A
the intrinsic pathway is slower and more complex; however both pathway converge at the common pathway
16
Q
where is the intrinsic pathway initiated?
A
in the bloodstream
17
Q
what is the intrinsic pathway?
A
a blood coagulation pathway that is initiated by surface contact damage to the vascular endothelium; activates clotting factors and blood clot formation
18
Q
what does APTT do?
A
evaluate the intrinsic pathway, which is initiated by contact with exposed collagen (from damage to endothelium)
19
Q
serum is the liquid that remains after the blood has clotted
A
20
Q
what happens in a plasma test?
A
anticoagulant is applied to the sample to prevent blood clotting, the cells are removed via coagulation
21
Q
what does the product of a plasma test contain?
A
it contains all the components of blood except the cells, including clotting factors
22
Q
what cells are removed in a sample during a plasma test?
A
red blood cells, white blood cells, and platelets
23
Q
what processes are included in haematopoiesis?
A
erythropoiesis, myelopoiesis, lymphopoiesis, and thrombopoiesis
24
who is myelopoiesis?
production of myeloid cells (specific type of white blood cells)
25
name some examples of myeloid cells
monocytes, macrophages, and granulocytes
26
where is the highest concentration of bone marrow?
the hip
27
what happens in cases where blood cells cannot be produced (e.g. bone marrow infiltration)?
extramedullary haematopoiesis may occur, cells can be produced in the liver or spleen (which can cause hepatosplenomegaly)
28
what does extramedullary?
external to the bone marrow
29
what does ontogeny mean?
origination and development of bone marrow
30
what are blood islands?
clusters of developing blood cells and blood vessels that form during embryonic development
31
what is the first site of blood cell and vessel formation?
blood islands
32
where and when do blood islands develop?
in yolk sacs, at around days 13-15 of gestation
33
what is definitive haematopoiesis?
production of HSCs, which maintain blood cell production
34
what is another term for definitive haematopoiesis?
long-term blood cell formation
35
where does definitive haematopoiesis come from?
a population of stem cells first discovered in the AGM (aorta-gonads-mesonephros) region in the dorsal aorta
36
what is the dorsal aorta?
the first functional intra-embryonic blood vessel
37
what are haemangioblasts?
progenitor cells in the developing embryo that have the ability to differentiate into both blood vessels (endothelial cells) and blood cells (haematopoietic cells)
38
where are haemangioblasts found?
in the AGM region during embryonic development
39
what is seeding?
the process by which haematopoietic progenitor cells migrate from their initial site of formation (e.g. AGM) to secondary haematopoietic organs (e.g. liver, spleen, bone marrow)
40
what is one of the first major organs to take on haematopoietic activity during development?
the liver
41
what happens after the AGM region produces haematopoietic progenitors, where do they go?
they migrate to the liver, where they establish the foetal haematopoietic niche
42
how long does the liver act as a haematopoietic organ?
until the bone marrow becomes the primary site for haematopoiesis later in foetal development
43
what organ is important for immune system development in foetal life?
spleen
44
compare the liver and spleen as sites of haematopoiesis?
the role of the spleen is less pronounced than the liver
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what do haematopoietic progenitors that migrate to the spleen do?
populate the organ with various blood cell lineages
46
when is the yolk sac the primary location of haematopoiesis?
during the first 2 months of foetal development
47
when is the liver/spleen the primary location of haematopoiesis?
between the first 2-7 months of a foetus' life
48
when does the bone marrow become the primary location of haematopoiesis?
during the first 5-9 months
49
where is the primary location of haematopoiesis in infants?
in the bone marrow of most bones
50
where is the primary location of haematopoiesis in adults?
vertebrae, ribs, sternum, skull, sacrum, pelvis, proximal ends of femur
51
what is indicated by immature cells being found outside the bone marrow?
sepsis/infection or leukaemia
52
what are blast cells?
intermediates in normal pathophysiology
53
what are the 4 main types of blasts?
- erythroblasts (erythrocyte pathway)
- lymphoblasts (lymphoid pathway)
- megakaryoblasts (platelet pathway)
- myeloblasts (myeloid pathway)
54
how are leukaemias and myeloproliferative pathways often diagnosed?
by an increase in specific lineage blast cells in blood
55
why shouldn't blast cells be found in blood?
because they are immature;
56
what does the presence of blast cells in blood indicate?
leukaemia, but not sepsis
57
what does it mean if larger forms of cells are found in the blood?
immature cells are present in the blood
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what is red cell leukaemia?
cancer of red blood cells, however it is rare
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what does red cell leukaemia entail?
abnormal growth of red blood precursors in bone marrow
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how many HSCs does the average adult have?
50,000
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what are the properties of zygotic stem cells?
totipotent and not self-renewing
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what are the properties of embryonic stem cells?
pluripotent and self-renewing
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what are the properties of multipotent stem cells?
multipotent and self-renewing
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what are the properties of progenitor cells?
have restricted differentiating potential and self-renewing
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what are the properties of immature differentiated cells?
have restricted differentiating potential and not yet functional
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what are the properties of mature differentiated cells?
non-diving and fully functional
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what does haematopoiesis begin with?
a pluripotent stem cells
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what kind of division do HSCs experience?
asymmetrical
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how rare are HSCs?
1 in every 20 million nucleated cells
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markers of HSCs
CD34+, CD38-, Lin-
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what does it mean to be CD34+?
marks early stem cells in bone marrow
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what does it mean to be CD38-?
suggests more primitive, less differentiated state
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what does it mean to be Lin-?
it means a cell has no lineage
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how does CD38 increase?
with differentiation
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where are HSCs produced?
in the red marrow
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what compartments make up the bone marrow?
red and yellow
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what is produced in red marrow?
red blood cells
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how many healthy blood cells can be produced by healthy yellow marrow?
5-10 x 10^11
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what does healthy yellow marrow possess?
a microniche environment
80
what is bone marrow made up of?
haematopoietic tissue, sinuses and non-haematopoietic tissues (e.g. fibroblasts which lead to collagen and macrophages)
81
what does it mean if there is little interstitial space in bone marrow?
it is hypercellular
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what can make bone marrow hypocellular?
chemotherapy
83
what are myeloproliferative disorders (MPDs)?
a group of blood cancers where the bone marrow produces too many blood cells
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what are growth factors?
naturally occurring proteins that act as chemical messengers
85
what do growth factors stimulate?
cell growth, proliferation, and differentiation
86
what are growth factors essential for?
wound healing, tissue repair, and maintaining the overall health of various tissues, including skin.
87
what does the extrinsic regulation of haematopoiesis involve?
cell to cell interactions and extracellular matrix environment regulators (e.g. cytokines)
88
what does the intrinsic regulation of haematopoiesis involve?
genetic events, transcription factors, and stage-specific cell cycle regulation
89
how do haematopoietic progenitors and megakaryocytes appear on blood films?
HPs are dark, and megakaryocytes are light pink
90
what are erythroblastic islands?
specialised microenvironments in the bone marrow for erythropoiesis
91
what do H&E stains of intertrabecular tissue show?
50% contains haematopoietic tissue, and the other 50% contains fat
92
what is an M:E ratio?
a comparison of relative proportions of granulocytic and erythrocytic cells
93
what is the average M:E ratio?
3:1
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what is the reference range for a M:E ratio?
2:1-4:1
95
what kind of environment does haematopoiesis occur in?
a suitable microenvironment (niche) provided by a stromal matrix, where stem cells can grow and divide
96
what may the niche where haematopoiesis occur be like?
either vascular (lined by endothelium) or endosteal (lined by osteoblasts)
97
what do stromal cells of bone marrow include?
adipocytes, fibroblasts, osteoclasts, endothelial cells, and macrophages
98
what are osteoblasts?
cells with a single nucleus that synthesise bone
99
what does G-CSF stand for
granulocyte colony-stimulating factor
100
what is a G-CSF?
a protein (specifically growth factor) that stimulates the bone marrow to produce more white blood cells, thus helping fight infection
101
what can regulate haematopoiesis?
cytokines (i.e., haematopoietic growth factors)
102
what are haematopoietic growth factors?
glycoprotein hormones that regulate the proliferation and differentiation of haematopoietic progenitor cells
103
what does EPO stand for?
erythropoietin
104
what is EPO?
a hormone (primarily produced by the kidneys) that stimulates bone marrow to produce RBCs
105
what does TPO stand for?
thyroid peroxidase
106
what is TPO?
an enzyme produced by the thyroid gland that produces thyroid hormones
107
aside from EPOs and TPOs, what is a major source of growth factors?
stromal cells
108
where may growth factors act?
locally (cell-to-cell contact) or they may circulate in plasma
109
what can transcription factors induce?
synthesis of proteins specific to cell lineages
110
what do haematopoietic stem cells use for intracellular transduction?
dimerisation
111
what is intracellular/signal transduction?
the process by which a cell converts a signal (e.g. a ligand binding to a receptor) to a functional response within the cell
112
what is the JAK/STAT pathway?
a key signalling mechanism used by many cytokine receptors in haematopoietic stem cells
113
give an example of 2 exemplar ligands that can bind to receptors
IL-3 and EPO
114
give the order of steps in the JAK/STAT pathway
1. ligand binds to a receptor, making the receptor dimerise
2. this brings JAKs together and they phosphorylate each other
3. then they phosphorylate specific tyrosine kinase residues on the receptor
4. these serve as docking sites for STAT proteins which bind, become phosphorylated by JAKS and then dimerise
5. once dimerised, they translocate to the nucleus where they bind to DNA and regulate the transcription of genes that control HSC processes
115
what does JAK stand for?
Janus kinase
116
what does STAT stand for?
Signal Transducer and Activator of Transcription
117
aside from JAK/STAT pathway, what other pathways impact HSCs?
MAPK (mitogen-activated protein kinase) and PI3K/AKT pathways
118
how many new erythrocytes are produced per day?
10^12
119
what is the life span of an erythrocyte?
120 days
120
what is the structure of an erythrocyte like?
very elastic (can become a third of its actual size in microvasculature system) and biconcave to increase cell surface area
121
what is the life span of an erythrocyte in haemolytic anaemia patients?
60 days
122
what can flow cytometry be used to differentiate?
between myeloblasts and pronormoblasts
123
why is it rare to find megakaryocytes in the blood?
because they too large to escape bone marrow
124
% proportion of EPO locations
90% in kidneys, 10% found in liver and elsewhere
125
what are the two reasons an adequate supply of platelets is needed?
1. to repair minute vascular damage that occurs in everyday life
2. initiates thrombus formation in the event of overt vascular injury
126
how are megakaryocytes formed?
from CFU-Meg by a process called endomitotic replication
127
what is another term of endomitotic replication?
endoreduplication
127
what is CFU?
a colony-forming unit
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what is endomitotic replication?
a type of cell cycle variation where the genome is replicated without subsequent cell division, leading to polyploidy
129
what is polyploidy?
increased DNA content
130
what is essential for platelet production?
TPO (thrombopoietin)
131
what occurs in endomitotic replication?
DNA replication and cytoplasmic expansion occurs, but not cell division
132
what does leaking of the vasculature manifest as?
petea and bruising
133
what makes people bruise easier?
having weak vasculature
134
what kinds of people have weak vasculature?
1. elderly people
2. people with liver disease
3. people with bleeding/clotting disorders
135
why do people with liver disease bruise easier?
they do not have sufficient TPO, and therefore not enough platelets
136
the bigger the nucleus, the ____ the platelets made from the cell
bigger
137
megakaryocyte carries more ____ than normal cells, therefore polyploidy occurs
chromosomes
138
what shape are banded neutrophils?
kidney-shaped
139
size of red blood cells
6-8 micrometres in diameter
139
what is GM-CSF?
granulocyte-macrophage colony-stimulating factor
139
what regulates granulocytes and monocytes?
IL-3 and GM-CSF
140
how do red blood cells appear on film?
orange-pink to rose (depending on stain)
141
what stain makes RBCs appear pink?
MGM (used in the UK)
142
what stain makes RBCs appear orange?
Wright stain (used in US)
143
function of RBCs
contains haemoglobin which transports oxygen from the lungs to the rest of the body
144
why do men have more erythrocytes?
they have more testosterone
145
give an example of a condition that can produce more erythrocytes
PCOS, as women with this condition have more testosterone
146
what can cause false diagnosis of polycythaemia vera?
dehydration means people have less plasma, which makes their haematocrit very high
147
what can kidney tumours cause excessive production of?
EPO
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what is a haematocrit also known as?
packed cell volume (PCV)
149
what do haematocrits measure?
% of RBCs in blood
150
how can mechanical heart structures affect red count?
it can reduce it by damaging RBCs passing through
151
reference value of RBCs in women
3.8-5.2 x 10^12/L
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what is polycythaemia vera (PV)?
blood cancer where the bone marrow produces too many RBCs, leading to thicker blood and potential complications like blood clots
153
what can high red cell count (polycythaemia) indicate?
PV, dehydration, hypoxia, and kidney tumour
154
what can low red cell count (anaemia) indicate?
nutrient deficiency, blood loss, increased haemolysis, hereditary disease, leukaemia
155
what is the average size of a platelet?
3-4 micrometres
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how do platelets appear on blood films?
red-purple surrounded by light blue
157
what is the function of platelets?
they are involved in the haemostatic response through the formation of the platelet plug to repair damaged blood vessels
158
what is a platelet plug?
a temporary, early-stage blood clot formed when platelets adhere, activate, and aggregate at the site of a blood vessel injury
159
what is haemostasis?
the body's natural process to stop bleeding after a blood vessel is damaged
160
what can thrombocytopaenia cause?
massive platelets, which can appear larger than RBCs
161
what is the lifespan of a neutrophil?
5 hours – 5 days, depending on activation
162
what is the size of an average neutrophil?
12-15 micrometres
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appearance of neutrophils
acidophilic cytoplasm with fine azurophilic (purple) granules; the nucleus has clumped chromatin (very dense) with 2- lobes
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what are the functions of neutrophils?
1. phagocytosis of bacteria and yeast
2. remove debris from circulation
165
what kind of neutrophils have more than 2-5 lobes?
hypersegmented
166
what is the lifespan of a lymphocyte?
~200 days
167
what is the size of a lymphocyte?
10-16 micrometres
168
appearance of lymphocytes
round blue nucleus with scanty pale blue cytoplasm
169
what is the function of lymphocytes?
- B lymphocytes produce antibodies
- T cells cooperate with antibody production (T helper cells) and destruction of infected cells (cytotoxic T cells)
170
lymphocytes have a tiny ___ and is mainly made up of its ____
cytoplasm, nucleus
171
can T cells and B cells be differentiated on a blood film?
no, so flow cytometry is required
172
why are blood films preferable over flow cytometry?
they are quicker and more available in hospitals
173
what is the life span of monocytes?
1-7 days
174
what is the size of a monocyte?
12-20 micrometres
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appearance of monocytes
glassy greyish-blue cytoplasm with fine azure granules, usually with some vacuolation
176
what is the nucleus of a monocyte like?
often lobulated with an irregular shape
177
what is the function of a monocyte?
- similar to neutrophil (phagocytoses bacteria and yeast, and removes debris)
- aids in haemostasis
- works along lymphocytes generating antibodies as a macrophage in tissues with APCs
- can release cytokines (e.g. interleukins), which stimulates the immune system
178
how do monocytes aid haemostasis?
by presenting tissue factor to instigate the cloting cascade
179
how long do monocytes spend in bone marow?
1-3 days
180
how long do monocytes spend in circulation?
8-78 hours
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how long do monocytes spend in circulation?
>80 days in tissues
182
what is the lifespan of eosinophils?
2-5 days
183
what is the size of eosinophils?
12-17 micrometres
184
what is the appearance of eosinophils?
pale blue cytoplasm rarely seen due to larger reddish-orange granules
185
what are the lobes of eosinophils like?
usually bi-lobed nucleus, occasionally trilobed
186
what is the function of an eosinophil?
protects against parasitic infection
187
how do eosinophils protect against parasitic infection?
its granules contain proteins and peroxidases that can break down the lipid bilayer of parasites, as well as have bactericidal and helminthotoxic properties
188
what is the life span of basophils?
1-2 days
189
what is the size of a basophil?
10-14 micrometres
190
appearance of a basophil
large purple-black granules, often obscuring the nucleus
191
what is the function of a basophil?
- it participates in hypersensitivity reaction, and releases histamine
- also can release heparin, so prevent coagulation
192
reference range of leukocytes
4.0-11.0 x10^9/L
193
what can cause high WBC count (leukocytosis)?
infection, leukaemia, stress on body, allergy, sepsis
194
give an example of stress on the body that can cause leukocytosis
women being in labour
195
what can cause low WBC count (leukocytopoenia)?
antibiotics, viral infections, chemotherapy, autoimmune disorders, leukaemia
