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Blood cells and haematopoiesis Flashcards

1
Q

What is haematopoiesis?

A

The process by which mature blood cells are generated from precursor cells.

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2
Q

What are the main components of blood by percentage?

A

Plasma: 55-60%
Cells (aka haematocrit): 40-50%

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3
Q

What does a blood sample consist of when separated?

A

Top layer: Plasma (55-60%)

Middle layer: White blood cells and platelets

Bottom layer: Red blood cells (haematocrit)

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4
Q

What is the most abundant type of blood cell?

A

Red blood cells (erythrocytes), making up ~45% of blood volume.

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5
Q

What is the concentration of red blood cells in the blood?

A

Approximately 4-6 x 10⁶/µL (~45% v/v).

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6
Q

What are platelets also known as, and what is their concentration in the blood?

A

Platelets are also known as thrombocytes, with a concentration of ~1.5 - 4 x 10⁵/µL.

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7
Q

What is the concentration of white blood cells in the blood?

A

Approximately 4-11 x 10³/µL (<1% v/v).

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8
Q

Where are red blood cells and platelets confined?

A

Red blood cells and platelets are confined to blood vessels.

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9
Q

What is the role of white blood cells, and where are they found?

A

White blood cells (leukocytes) are part of the immune system and are in transit to/from tissues.

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10
Q

When does haematopoiesis begin in the developing fetus?

A

At 2–2.5 weeks in utero.

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11
Q

What are blood islands and where do they form?

A

Blood islands are distinct areas where blood cells begin to form, surrounded by mesenchyme and enveloped by endothelial cells.

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12
Q

What structures surround the blood islands during haematopoiesis?

A

The mesenchyme surrounds the blood islands.

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13
Q

What is the role of endothelial cells in blood island formation?

A

They arrange spatially to group blood cells in the lumen of primitive blood vessels.

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14
Q

what is the process of haematopoiesis

A

Stage A: Mesenchyme cells cluster to form blood islands.
Stage B: Endothelial cells surround the blood islands, differentiating into a vascular structure.
Stage C: Primitive blood cells group within the lumen of developing blood vessels, completing the initial formation of blood and vessel structure.

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15
Q

What is the primary site of haematopoiesis during the early prenatal period?

A

The yolk sac.

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16
Q

Which organs take over haematopoiesis after the yolk sac during the prenatal period?

A

The liver and spleen.

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17
Q

When does the bone marrow become the primary site of haematopoiesis?

A

Around month 7 of fetal development.

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18
Q

What happens to haematopoiesis sites postnatally?

A

Bone marrow in larger bones (e.g., vertebrae, pelvis, sternum, ribs) becomes the main site of haematopoiesis.

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19
Q

What is a totipotent stem cell?

A

A stem cell that can divide to produce all differentiated cells of an organism, including the zygote.

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20
Q

What is a pluripotent stem cell?

A

A stem cell that can divide into any of the three germ layers: endoderm, mesoderm, and ectoderm. All blood cells arise from a common pluripotent stem cell.

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21
Q

What is a multipotent stem cell?

A

A stem cell capable of dividing into multiple, but restricted, cell types.

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22
Q

What is a unipotent or progenitor cell?

A

A cell restricted to a single lineage, regulated by lineage-specific growth factors. It does not have the potential for self-renewal.

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23
Q

What are haematopoietic stem cells?

A

Stem cells that give rise to all circulating blood cells.

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24
Q

What are the 4 stages of haematopoiesis?

A
  1. Self-renewal: Maintained by stem cells.
  2. Committed cells: Progenitor cells form specific lineages.
  3. Developmental pathway: Precursor cells undergo differentiation.
  4. Differentiated functional cells: Mature cells carry out specialized functions in blood and tissue.
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25
Q

Why is it difficult to visually discern stem cell niches in bone marrow?

A

Bone marrow does not exhibit clear structural characteristics to define stem cell niches. The orchestration of stem cell activation and their interactions with adjacent cells occur temporally rather than structurally.

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26
Q

What is the primary blood supply to the bone marrow?

A

The nutrient artery is the primary blood supply to the bone marrow.

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27
Q

Where is bone marrow located in the body?

A

Bone marrow is located in the central medullary cavity of bones.

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28
Q

Describe the pathway of the nutrient artery in the bone marrow.

A
  1. The nutrient artery crosses the cortex through the nutrient canal into the medullary cavity.
  2. It divides into ascending and descending arteries, from which radial arteries arise.

3.Radial arteries enter the cortex through the endosteum and become cortical capillaries.

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29
Q

How does blood flow through the bone marrow?

A
  1. Blood from cortical capillaries mixes with periosteal and endosteal capillary blood.
  2. It then enters the medullary vascular sinuses, forming a dense network.
  3. Blood collects in the central sinus and exits the bone marrow.
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30
Q

What structures line the medullary vascular sinuses?

A

The sinuses are lined by endothelial cells and surrounded by adventitial reticular cells.

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31
Q

Where does haematopoiesis occur in the bone marrow?

A

Haematopoiesis occurs in the extravascular spaces between the medullary vascular sinuses.

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32
Q

What is the multipotential stem cell responsible for haematopoiesis called?

A

The multipotential haematopoietic stem cell (hemocytoblast).

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33
Q

What are the two main progenitor cell lineages that arise from a haematopoietic stem cell?

A

Common myeloid progenitor
Common lymphoid progenitor

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34
Q

What is the shape and diameter of red blood cells (RBCs)?

A

RBCs are biconcave discs with a diameter of 7 µm.

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35
Q

What organelles are ABSENT in red blood cells?

A

Red blood cells lack a:
- nucleus
- mitochondria
- Golgi apparatus
- ribosomes/mRNA.

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36
Q

What is the primary protein found in RBCs?

A

Haemoglobin

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37
Q

What type of metabolism do RBCs rely on and why?

A

Anaerobic metabolism of glucose because they lack mitochondria.

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38
Q

What is the lifespan of an RBC?

A

Approximately 120 days.

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39
Q

How are old RBCs removed from the body?

A
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40
Q

At what rate are RBCs replaced in the body?

A

RBCs are replaced at a rate of 10^10 per hour.

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41
Q
A
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42
Q

Where are erythroid precursor cells found?

A

In the bone marrow.

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43
Q

What is the penultimate precursor of red blood cells?

A

The normoblast.

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44
Q

What are the key features of a normoblast?

A

Diameter: 8-10 µm
Highly condensed nucleus
Contains most of the haemoglobin
Retains a few mitochondria and ribosomes

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45
Q

What happens to the nucleus of the normoblast during RBC production?

A

The nucleus is ejected.

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46
Q

What stage follows the normoblast in RBC production?

A

The cell enters the blood as a reticulocyte.

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47
Q

How long does it take for a reticulocyte to mature into a red blood cell?

A

1-2 days.

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48
Q

What percentage of red blood cells in the blood are reticulocytes?

A

Approximately 1%.

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49
Q
A
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50
Q

What is anaemia?

A

A condition caused by an insufficient number or impaired function of red blood cells.

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51
Q

What are the normal haemoglobin levels in men and women?

A

Men: 13.5-17.5 g/dl
Women: 12.0-15.5 g/dl

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52
Q

What percentage of the global population is affected by anaemia?

A

One-third of the global population.

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53
Q

What are the main causes of anaemia?

A
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54
Q

what are the symptoms of anemia

A
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55
Q

what are the 4 treatments for anemia

A

iron salts

folic acid

vitamin B12

epoietin

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56
Q

What are iron salts used for in anaemia treatment?

A

Iron salts treat iron deficiency caused by chronic blood loss, increased demand, inadequate diet, or inadequate absorption.

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57
Q

What is folic acid used to treat in anaemia?

A

Folic acid treats megaloblastic anaemia caused by poor diet, malabsorption syndromes, and drugs. It is also used to manage folate deficiency in pregnancy, premature births, and chronic haemolytic anaemias (e.g., sickle cell).

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58
Q

When is folic acid given in the context of drug toxicity?

A

It is used to counter toxicity from methotrexate, a folate antagonist.

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59
Q

What is Vitamin B12 used for in the treatment of anaemia?

A

It treats pernicious anaemia and Vitamin B12 deficiency. It is also given prophylactically after surgery when intrinsic factor production is removed (e.g., stomach surgery) or absorption is impaired (e.g., terminal ileum issues).

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60
Q

What is epoietin and when is it used?

A

Epoietin is used for anaemias caused by renal failure, chemotherapy, AIDS, and chronic inflammatory conditions. It also increases the yield of autologous blood before donation and prevents anaemia in premature infants reacting to unpreserved milk formulations.

61
Q

What happens when blood samples from incompatible groups are mixed?

A

Red cells stick together as clumps, a process called agglutination.

62
Q

What causes agglutination in blood groups?

A

occrus when the blood groups are incompotaible which is caused by antigens on the red cell membrane reacting with antibodies in the plasma.

63
Q

What happens if the titre of antibodies is high in incompatible blood groups?

A

Antibodies bind to antigens on several red cells, gluing them together and causing haemolysis (rupture).

64
Q

What are the consequences of agglutination following a blood transfusion?

A

It can lead to anaemia and other serious complications.

65
Q

What are antigens in blood groups mostly made of?

A

Glycolipids, though they are also found in other tissues.

66
Q

What are the two most important blood group systems?

A

The ABO system and the Rh (Rhesus) groups.

67
Q

What are the four groups in the ABO blood group system?

A
68
Q

Who are universal recipients and why?

A

AB individuals, because they have no antibodies in their plasma.

69
Q

Who are universal donors and why?

A

O individuals, because their red cells have no antigens.

70
Q

What blood types and antibodies are present in the ABO system?

A

Agglutinogens: Antigens on red blood cells (e.g., A and B).
Agglutinins: Antibodies in the plasma (e.g., Anti-A and Anti-B).

71
Q

How are blood groups determined genetically?

A

A and B are dominant.
O is recessive.
Genotypes AO and AA both result in blood group A.

72
Q

What is the racial distribution of blood groups?

A
73
Q

What are the safe transfusions in the ABO system?

A
74
Q

What are the two groups in the Rh (Rhesus) system?

A

Rh+ and Rh-.

75
Q

What defines Rh+ and Rh-?

A

Rh+: Has the D antigen on red cell membranes.

Rh-: Does not have the D antigen.

76
Q

How is the Rh system genetically determined?

A

The D gene is dominant.
The d gene (allelomorph) is recessive.

77
Q

What percentage of the population is Rh+?

A

Approximately 85%.

78
Q

Are antibodies to the D antigen (anti-D agglutinin) normally found in Rh- individuals?

A

No, these antibodies are only produced after exposure to the D antigen.

79
Q

in what 2 ways can exposure to the D antigen occur?

A

During transfusion with Rh+ blood.

When an Rh- mother has an Rh+ fetus, and fetal red cells enter the maternal circulation during birth.

80
Q

What is a major complication for an Rh- mother with an Rh+ fetus?

A

Haemolytic disease in the next child during pregnancy due to sensitization from the first Rh+ child.

81
Q

What is a major risk of blood type incompatibility during transfusion?

A

Haemolytic transfusion reaction caused by recipient antibodies (α, β, or anti-D) reacting with donor red cell antigens.

82
Q

What happens if haemolysis occurs during a blood transfusion?

A

Accumulation of bilirubin may lead to haemolytic jaundice.

Severe cases can result in renal failure.

83
Q

Why are donor antibodies usually not a problem in blood transfusions?

A

Donor antibodies are typically diluted or removed during the process.

84
Q

What infections can be transmitted through blood transfusions?

A

Hepatitis
HIV
Prions
Malarial parasites

85
Q

What are potential non-infectious complications of blood transfusions?

A
86
Q

What are platelets derived from?

A

Platelets are produced in the bone marrow (BM) from megakaryocyte precursors via thrombopoietin

87
Q

Describe the structure and lifespan of platelets.

A

Structure: Anuclear, discoid shape, 2-4 µm diameter.
Lifespan: Approximately 8-12 days.

88
Q

What are the 2 primary functions of platelets?

A

Haemostasis: Blood clotting and maintenance of blood vessels.

Platelets adhere to fibrin filaments and damaged endothelial surfaces, forming a platelet clot.

89
Q

What is unique about protein synthesis in platelets?

A

Platelets have limited de novo protein synthesis but can secrete mediators stored in:

α granules
Dense granules
Liposomes

90
Q

How are platelets linked to innate immunity?

A

Platelets connect haemostasis to:

Controlling blood loss.
Fighting invading pathogens.

91
Q

whats the name of these 3 stages of platelet shape change

A
92
Q

What are megakaryocytes?

A

Giant cells (50–75 µm in diameter) with a single, large, irregular nucleus.

93
Q

What unique process do megakaryocyte progenitors undergo?

A

Progenitors undergo up to 5 repeated cell cycles without an intervening mitosis.

94
Q

How is the cytoplasm of megakaryocytes organized for platelet formation?

A

The cytoplasm is partitioned into 2-4 µm packages by vesicles of the endoplasmic reticulum (ER), called platelet demarcation channels.

95
Q

How are platelets released from megakaryocytes?

A

Vesicles of the endoplasmic reticulum (ER) fuse, ejecting the platelets.

96
Q

What percentage of circulating leukocytes are neutrophils?

A

Neutrophils constitute 60% of circulating leukocytes.

97
Q

How many neutrophils are produced and released daily under basal conditions?

A

Approximately 10¹¹ neutrophils are produced and released daily from the bone marrow.

98
Q

What is the half-life of neutrophils in the blood?

A

The half-life of neutrophils in the blood is 6.7 hours.

99
Q

What does “polymorphonuclear (PMN)” mean in relation to neutrophils?

A

It refers to their multi-lobed nucleus. Neutrophils are fully differentiated and cannot multiply, with limited capacity for protein synthesis.

100
Q

What is the primary function of neutrophils?

A

Clearing pathogens during infection and responding to chemotactic signals to sites of inflammation.

101
Q

What is the role of neutrophils in inflammation?

A

Neutrophils are the first cell type recruited to the site of inflammation.

102
Q

What is the negative effect of neutrophils in chronic inflammatory diseases?

A

Neutrophils can damage healthy tissue in diseases like rheumatoid arthritis (RA), multiple sclerosis (MS), and chronic obstructive pulmonary disease (COPD).

103
Q

what are the constituents of human neutrophil granules

A
104
Q

What is the primary mechanism by which neutrophils chase bacteria?

A

Chemotaxis – movement in response to a chemical gradient.

105
Q

What cellular structures are involved in neutrophil motility?

A

Pseudopods (extensions of the cell membrane) and uropod (trailing edge of the cell).

106
Q

give examples of Neutrophil chemokines

A
107
Q

What energy pathways do neutrophils primarily rely on?

A

Glycolysis and the hexose monophosphate pathway.

108
Q

What structural feature allows neutrophils to store energy?

A

Sparse organelles, but they have abundant glycogen.

109
Q

What are the primary functions of neutrophils?

A

Phagocytosis (engulfing pathogens) and being highly motile to reach infection sites.

110
Q

Name three types of receptors found on neutrophils.

A

Receptors for bacterial polysaccharides, complement factors, and the Fc portion of antibodies.

111
Q

How do neutrophils kill ingested microorganisms?

A

Through hydrolytic enzymes and reactive oxygen species (ROS) generated by a respiratory burst involving NADPH oxidase and myeloperoxidase.

112
Q

What happens to neutrophils after a single burst of activity?

A

They die due to their limited synthetic capabilities.

113
Q

What is the main cellular constituent of pus?

A

Neutrophils.

114
Q

What percentage of leukocytes do eosinophils comprise under basal conditions?

A

1% of circulating leukocytes.

115
Q

What is a distinguishing feature of the eosinophil nucleus?

A

Bi-lobed nucleus (polymorphonuclear).

116
Q

What are eosinophils motile to?

A
117
Q

What is the primary function of eosinophils?

A

Extracellular killing of parasites.

118
Q

What diseases are eosinophils associated with?

A

Eosinophil-associated gut diseases
Hypereosinophilic syndromes
Allergy, asthma, and rhinitis

119
Q

What are eosinophils attacking in the image provided?

A

Eosinophils attacking a Schistosome larva

120
Q

How soon do eosinophils leave circulation after release from the bone marrow?

A

Within 8-12 hours.

121
Q

Where do eosinophils preferentially migrate under normal circumstances

A

The gastrointestinal tract or sites of inflammation.

122
Q

What is the typical lifespan of eosinophils in tissues?

A

Several days

123
Q

What conditions cause a significant increase in eosinophil numbers?

A

Parasitic infections

Allergic states, including asthma.

124
Q

Name the 4 cytotoxic secretory products of eosinophils and their functions.

A
125
Q

What is the size of monocytes, the largest leukocyte?

A

Up to 20 μm in diameter.

126
Q

Describe the shape of a monocyte’s nucleus.

A

Horseshoe-shaped or kidney-shaped.

127
Q

What are the 2 key functions of monocytes?

A

Highly phagocytic

Motile

128
Q

When do monocytes leave the blood after being released from the bone marrow?

A

Within 2 days.

129
Q

What do monocytes become after entering tissues?

A

They differentiate into macrophages.

130
Q

What is the lifespan of macrophages derived from monocytes?

A

Months to years.

131
Q

what are the 4 functions of macrophages

A
  1. Defense against micro-organisms.
  2. refuse collection
  3. antigen presentation
  4. cytokine secretion
132
Q

What do macrophages remove as part of their “refuse-collection” function?

A

Removal of tissue debris, old red blood cells, etc

133
Q

How do macrophages contribute to antigen presentation?

A

By displaying proteolytic fragments of ingested antigens on their surface to trigger an immune response from T lymphocytes.

134
Q

What role do macrophages play in cytokine secretion?

A

They regulate haemopoiesis by secreting cytokines like IL-1, IL-6, IL-9, and GM-CSF.

135
Q

What is the diameter of small lymphocytes?

A

6–9 µm.

136
Q

What percentage of the cell is occupied by the nucleus in small lymphocytes?

A

The condensed nucleus occupies 90% of the cell.

137
Q

What is the main function of small lymphocytes?

A

Responsible for adaptive immunity.

138
Q

Into which two cell types are small lymphocytes subdivided?

A

B cells and T cells.

139
Q

What is the diameter of large lymphocytes?

A

9–15 µm.

140
Q

What percentage of lymphocytes do large lymphocytes make up?

A

Approximately 3%.

141
Q

What is the role of most large lymphocytes?

A

They are activated B cells in transit to tissues to become plasma cells.

142
Q

What is the function of natural killer (NK) cells?

A

NK cells kill virus-infected or tumor cells using a mechanism that does not involve specific antigens.

143
Q

What is the role of B lymphocytes?

A

B lymphocytes respond to antigens by proliferating and maturing into plasma cells, which secrete the same immunoglobulin (antibody).

144
Q

What receptor is present on the surface of B lymphocytes?

A

Surface immunoglobulin (receptor for antigen).

145
Q

What receptor is present on the surface of T lymphocytes?

A

T cell receptor (TCR) for antigens.

146
Q

Into what two main types are T lymphocytes subdivided?

A

Helper T cells and Cytotoxic T cells.

147
Q

What marker is expressed by Helper T cells, and what is their function?

A

CD4 marker. Helper T cells secrete cytokines to assist other lymphocytes.

148
Q

What marker is expressed by Cytotoxic T cells, and what is their function?

A

CD8 marker. Cytotoxic T cells kill virus-infected cells.

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