WEEK 2 (PART 1) Flashcards
1
Q
What are the main stages of new blood cell production (haematopoiesis)?
A
- Cellular proliferation * Differentiation from stem cell to mature cell * Cell morphological changes specific to each cell type * Functional maturation of cells * Cell death
2
Q
Where does haematopoiesis begin in the embryo?
A
Blood islands of the yolk sac (mesoblastic period)
3
Q
When does the mesoblastic period occur and what is its primary function?
A
19-20 days of gestation, mainly red blood cell production (erythropoiesis)
4
Q
When and where does the hepatic period of haematopoiesis begin?
A
5th-6th week of gestation, fetal liver
5
Q
What cell type is minimally produced in the fetal liver?
A
Leukocytes
6
Q
When do the spleen, thymus, and lymph nodes become involved in haematopoiesis?
A
Around the same time the fetal liver starts (5th-6th week)
7
Q
When and where does the myeloid period of haematopoiesis begin?
A
5th month of gestation, bone marrow
8
Q
When does the bone marrow become the sole site of blood cell production (under healthy conditions)?
A
3 weeks after birth
9
Q
What is extramedullary haematopoiesis?
A
Blood cell production in liver and spleen (outside bone marrow) due to bone marrow dysfunction
10
Q
Why might the spleen and liver resume blood cell production in adults?
A
When bone marrow cannot meet the body’s demands due to pathology
11
Q
How does the capacity for extramedullary haematopoiesis change with age?
A
Decreases with age as bone marrow matures
12
Q
What happens to red bone marrow as we age?
A
Replaced by yellow (fatty, inactive) bone marrow
13
Q
Where are the active sites of haematopoiesis located in adult bones?
A
Pelvis, vertebrae, ribs, sternum, skull, and proximal ends of long bones
14
Q
Can yellow bone marrow become active again?
A
Yes, it can be reactivated to become red marrow
15
Q
What are the main components of bone marrow?
A
- Blood vessels * Nerves * Blood cells (differentiated and undifferentiated) * Niche cells (supporting blood cell development) * Bone stromal cells * Venous sinusoids (specialized for blood cell release)
16
Q
What is the main function of erythrocytes (red blood cells)?
A
Oxygen delivery to tissues
17
Q
Where do erythrocytes originate from?
A
Colony-forming unit stem cells
18
Q
What are the early precursors to erythrocytes called?
A
Erythroid progenitor cells
19
Q
Where do erythrocytes mature?
A
Bone marrow
20
Q
What is the first nucleated stage of erythrocyte development?
A
Proerythroblast
21
Q
What does a proerythroblast produce?
A
Hemoglobin and other proteins (using ribosomes)
22
Q
What is the next stage of development after a proerythroblast?
A
Reticulocyte (immature red blood cell)
23
Q
What is a key feature of a mature erythrocyte?
A
Lacks a nucleus (anuclear)
24
Q
What is the shape of a mature erythrocyte?
A
Biconcave disc
25
How does the shape of an erythrocyte help with its function?
Allows it to deform and squeeze through narrow capillaries
26
What benefit does the biconcave shape provide for gas exchange?
Increases surface area to volume ratio, maximizing gas diffusion
27
What is the function of hemoglobin (Hb) in red blood cells?
Carries oxygen
28
What is the basic structure of a hemoglobin molecule?
* Two pairs of polypeptide chains (globins) * Four iron-containing complexes (hemes)
29
How do different types of hemoglobin vary?
Primarily in the type of polypeptide chains (alpha, beta, gamma, delta, epsilon, or zeta)
30
What is the most common type of hemoglobin in adults?
Hemoglobin A (HbA)
31
What are the polypeptide chains in Hemoglobin A?
Two alpha (α) and two beta (β) chains (α2β2)
32
What is a fetal type of hemoglobin with high oxygen binding affinity?
Hemoglobin F (HbF)
33
What are the polypeptide chains in Hemoglobin F?
Two alpha (α) and two gamma (γ) chains (α2γ2)
34
How does carbon monoxide (CO) affect hemoglobin?
It competes with oxygen for binding sites on the iron ion, but with a stronger affinity
35
What is the main factor controlling erythropoiesis (red blood cell production)?
Feedback loop involving erythropoietin (EPO)
36
What stimulates EPO production?
Low blood oxygen levels (anemia, high altitude)
37
How does the body sense low blood oxygen?
Chemoreceptors in the carotid body and aortic arch signal the brain
38
Where is EPO produced?
Primarily by kidneys, with some from the liver
39
What is the target of EPO in the bone marrow?
Niche and hematopoietic stem cells (HSCs)
40
What is the primary function of EPO?
Stimulates proliferation and differentiation of red blood cell precursors
41
Why is erythropoiesis a high-energy process?
RBCs need energy to maintain cell membrane and keep hemoglobin in its reduced state for oxygen binding
42
What are the two vulnerable sites in hemoglobin for oxidation?
Iron atom in the heme ring and sulfhydryl groups on the globin chain
43
What happens when the iron atom in hemoglobin is oxidized?
It forms methemoglobin, which cannot carry oxygen
44
What is the main energy source for red blood cells?
Glucose
45
How do red blood cells generate energy since they lack mitochondria?
* Embden-Meyerhof Pathway (anaerobic): converts glucose to lactate for ATP production * Hexose monophosphate shunt (oxidative pathway): generates NADPH to maintain reduced state of hemoglobin
46
What is the lifespan of a red blood cell?
Approximately 120 days
47
Where are red blood cells destroyed?
Reticuloendothelial system (spleen being the major site)
48
What is a potential consequence of a splenectomy (spleen removal)?
Reduced ability to destroy old red blood cells and fight encapsulated bacteria
49
What are leukocytes (WBCs)?
Nucleated blood cells involved in immune defense
50
Where are leukocytes found?
* Bone marrow * Peripheral blood * Tissues (spend most of their time here)
51
How many main types of leukocytes are there?
5: neutrophils, basophils, eosinophils, monocytes, and lymphocytes
52
How are leukocytes classified based on granularity?
* Granulocytes (have visible granules): neutrophils, eosinophils, basophils * Non-granulocytes (no visible granules): monocytes, lymphocytes
53
How are leukocytes classified based on nuclear shape (when mature)?
* Polymorphonuclear cells (multi-lobed nucleus): neutrophils, eosinophils, basophils * Mononuclear cells (single nucleus): monocytes, lymphocytes
54
What are neutrophils?
Most common type of leukocyte (white blood cell)
55
Where are neutrophils found?
Peripheral blood
56
What is the lifespan of a neutrophil?
9-10 days
57
What are the stages of neutrophil development?
Myeloblast, promyelocyte, myelocyte, metamyelocyte, band, segmented
58
How do neutrophils leave the bloodstream?
Diapedesis (passing between endothelial cells)
59
What is a main function of neutrophils?
Protecting against infection through phagocytosis
60
What is the significance of band forms in blood tests?
Presence of band forms suggests acute inflammation
61
What is the main energy source for neutrophils?
Anaerobic glycolysis (like red blood cells)
62
What are the steps of phagocytosis by neutrophils?
1. Motility: Induced by chemotaxis from injured tissue
2. Recognition: Binding to antibodies and complement proteins (opsonins) on foreign particles
3. Ingestion: Fusion of the neutrophil with the foreign particle to form a phagosome
4. Degranulation: Release of digestive enzymes from neutrophil granules into the phagosome
5. Killing: Production of toxic metabolites (superoxide anion and hydrogen peroxide) to kill the ingested particle
63
What are eosinophils?
A type of leukocyte (white blood cell)
64
Where are eosinophils drawn to?
Sites of allergic reactions (hypersensitivity)
65
How do eosinophils help fight parasites?
They can damage the larval stage of parasitic worms.
66
What is the lifespan of an eosinophil?
Only 18 hours
67
What is the main energy source for eosinophils?
Glycolysis (like neutrophils)
68
What do eosinophil granules contain?
* Hydrolytic enzymes for digestion * Peroxidase (an enzyme in higher concentration than in neutrophils)
69
What are basophils?
The least common type of leukocyte (white blood cell)
70
Where are basophils formed?
Bone marrow
71
Where do basophils migrate?
Tissues
72
How are basophils similar to mast cells?
They share some resemblance but are distinct cell types
73
What is the lifespan of a basophil?
Short (similar to eosinophils)
74
What potential role do basophils play?
Managing parasitic infections
75
Where are basophils recruited to?
Sites of allergic reactions
76
What do basophils secrete during allergic reactions (similar to mast cells)?
Histamine
77
What molecule triggers degranulation (release of contents) in basophils during allergic reactions?
IgE (same as mast cells)
78
Examples of conditions where basophils are involved:
* Bronchial asthma * Urticaria (hives) * Allergic rhinitis * Anaphylaxis
79
What is the main function of monocytes?
Phagocytosis
80
What other immune system roles do monocytes play?
Cellular and humoral immunity
81
What happens to monocytes when they migrate from blood to tissues?
They become macrophages
82
What is the main energy source for monocytes?
Aerobic glycolysis (for phagocytosis)
83
What is the main energy source for macrophages?
Anaerobic glycolysis
84
What do mature monocytes contain to aid phagocytosis?
Lysosomal enzymes
85
What conditions can cause monocytosis (increased monocytes in blood)?
* Similar conditions that cause neutrophilia * Tuberculosis * Subacute bacterial endocarditis * Syphilis * Glucocorticoid administration * Overwhelming infections
86
Can monocytosis be benign or malignant?
Yes, it can be reactive (benign) or malignant
87
Where do lymphocytes originate?
Primary lymphoid organs (bone marrow, thymus)
88
What is the fate of mature lymphocytes?
Proliferation, differentiation, function, then apoptosis (programmed cell death)
89
Where do lymphocytes mature further and learn self-tolerance?
Secondary lymphoid organs (lymph nodes, spleen, tonsils, Peyer's patches)
90
What is the main function of lymphocytes?
Immune response: antigen recognition and controlled immune response generation
91
What are the main types of lymphocytes?
* B cells * T cells * Natural Killer (NK) cells
92
How are lymphocytes different?
Maturation process, cell markers, response to stimulation (though similar in morphology)
93
Can lymphocytes move between blood and tissues?
Yes
94
Is lymphocyte development dependent on antigens?
No, lymphopoiesis is continuous
95
What happens to lymphocytes in secondary lymphoid organs?
They are educated to not attack self-antigens and become immunocompetent upon antigen encounter
96
What are some infectious causes of lymphocytosis?
* Epstein-Barr virus (infectious mononucleosis) * Cytomegalovirus infection * Bordetella pertussis (whooping cough) * Toxoplasmosis
97
What are some malignant causes of lymphocytosis?
* Chronic lymphocytic leukemia * Acute lymphoblastic leukemia
98
What can cause transient lymphopenia (low lymphocyte count) and neutropenia (low neutrophil count)?
Measles, mumps, chickenpox (followed by lymphocytosis as part of the immune response)
99
How are platelets formed?
The exact process is not fully understood, but they are fragments of cytoplasm from megakaryocytes (which develop from hematopoietic stem cells).
100
What is the shape and size of a platelet?
Flat disc, 1-2 microns in diameter
101
What is a key feature of platelets?
They lack a nucleus but have a complex surface
102
Where are platelets normally found?
Circulating in the blood
103
What happens to platelets when there is an injury?
They change shape, interact with the damaged blood vessel lining, and form a plug to stop bleeding.
104
What are some functions of platelets?
* Adhere to the injured vessel wall * Aggregate (clump together) * Swell to form a seal * Secrete compounds that help form a blood clot
105
What is the first response to a blood vessel injury (A)?
Vasoconstriction (blood vessel narrowing) to reduce blood flow at the injury site.
106
What causes vasoconstriction (A)?
Local neurohumoral factors released at the injury site.
107
How do platelets form a plug (B)?
* Platelets adhere to exposed tissue using von Willebrand factor (vWF). * Platelets become activated, change shape, and release granules. * Released ADP and thromboxane A2 (TxA2) cause further platelet aggregation (clumping).
108
What is the main component of the primary hemostatic plug (B)?
Aggregated platelets.
109
What triggers the coagulation cascade (C)?
Tissue factor and platelet phospholipids after platelet activation.
110
What is the role of the coagulation cascade (C)?
To form fibrin, a protein mesh that strengthens the clot.
111
How does fibrin strengthen the clot (C)?
Fibrin polymerizes (forms strands) around platelets, creating a stronger barrier.
112
What are some counterregulatory mechanisms that limit clot formation (D)?
* Tissue-type plasminogen activator (t-PA) breaks down clots. * Thrombomodulin on endothelial cells inhibits the coagulation cascade.
113
What is the difference between primary and secondary hemostasis?
* Primary hemostasis involves platelets forming a plug. * Secondary hemostasis involves the coagulation cascade forming a fibrin clot.
114
Do primary and secondary hemostasis occur sequentially?
No, they overlap functionally.
115
What happens when a blood sample is centrifuged?
It separates into layers based on component density.
116
What is the composition of the bottom layer (red)?
Erythrocytes (red blood cells).
117
What is the name of the middle layer (white)?
Buffy coat.
118
What is in the buffy coat?
Leukocytes (white blood cells) and platelets.
119
What is the composition of the top layer (yellowish liquid)?
Plasma.
120
Why might FBE results vary slightly between labs?
Different regions, instruments, or methods can be used.
121
What are the typical components measured in a full blood examination (FBE)?
* Hemoglobin concentration * Erythrocyte count (number of red blood cells) * Leukocyte count (number of white blood cells) * Platelet count * Differential white blood cell count (estimates of major leukocyte types)
122
What is the normal hemoglobin reference range for men (g/L)?
135 – 175 g/L
123
What is the normal hemoglobin reference range for women (g/L)?
115 – 155 g/L
124
What is the main function of hemoglobin?
Binds and transports oxygen to tissues throughout the body.
125
What can happen if a person has low hemoglobin (anemia)?
Tissues may not receive enough oxygen to function properly.
126
What is a potential cause of low hemoglobin?
Iron deficiency in the diet
127
What does red blood cell count estimate?
The number of red blood cells in circulation
128
Typical red blood cell count in adults (million cells/microliter):
* Men: 5.4 million * Women: 4.8 million (slightly lower due to physical and physiological differences)
129
What is the lifespan of a red blood cell?
Approximately 120 days
130
Where are red blood cells destroyed?
Primarily by the spleen
131
What is PCV (packed cell volume) or Hct (hematocrit)?
The proportion of red blood cells in whole blood.
132
What can affect PCV/Hct levels (other than red blood cell count)?
Fluid intake: * Dehydration can increase PCV/Hct. * Overhydration can decrease PCV/Hct.
133
What does MCV measure?
The average volume or size of red blood cells (erythrocytes).
134
Why is the biconcave shape of erythrocytes important?
* Allows them to squeeze through narrow capillaries. * Slows them down in capillaries for efficient oxygen and carbon dioxide exchange.
135
How does MCV change with erythrocyte age?
Young erythrocytes tend to be slightly larger than older ones due to aging and deformation.
136
What can a decreased MCV indicate?
Iron deficiency anemia (smaller red blood cells).
137
What can an increased MCV indicate?
Megaloblastic anemia caused by deficiencies in vitamin B12 or folate (larger red blood cells due to problems with DNA synthesis).
138
What does MCH represent?
The average amount of hemoglobin in one red blood cell.
139
What factors influence MCH?
* Mean cell volume (MCV) * Iron availability for hemoglobin formation
140
How does MCV influence MCH?
Larger erythrocytes (higher MCV) tend to have more hemoglobin.
141
How does iron deficiency affect MCH?
Less iron can lead to less hemoglobin per red blood cell (lower MCH).
142
How is MCHC calculated?
Hemoglobin level divided by PCV
143
What does MCHC represent?
The average concentration of hemoglobin within a red blood cell.
144
How is MCHC different from MCH?
MCHC considers the size of red blood cells (unlike MCH).
145
What does reticulocyte count measure?
The number of immature red blood cells (reticulocytes) in circulation.
146
Are reticulocytes normally seen in healthy adults?
Rarely.
147
What can a high reticulocyte count indicate?
* Increased red blood cell production due to conditions like anemia. * Certain blood cancers (leukemias).
148
Where are red blood cells produced?
Bone marrow.
149
What is the process of red blood cell production called?
Erythropoiesis.
150
What hormone stimulates erythropoiesis?
Erythropoietin.
151
Where is erythropoietin produced?
Primarily in the kidneys.
152
How do kidneys regulate erythropoietin production?
* Oxygen sensors in the kidneys detect blood oxygen levels. * Low blood oxygen levels trigger increased erythropoietin production.
153
How can anemia be classified?
By cause (etiology) and red blood cell appearance (morphology).
154
What is the main consequence of anemia?
Reduced oxygen delivery to tissues (tissue hypoxia).
155
How does the body compensate for anemia?
* Increased cardiac output (heart pumps more blood). * Increased erythropoietin (EPO) production to stimulate red blood cell production.
156
What are some clinical signs of severe anemia?
* Pale skin (pallor) due to less hemoglobin carrying oxygen. * Leg cramps. * Dizziness. * Breathlessness. * Fatigue. * In extreme cases: coma and death.
157
Normal WBC count in adults (per microliter)?
5,000-10,000
158
What does an elevated WBC count often indicate?
Inflammation or infection
159
What can a decreased WBC count indicate?
* Decreased production in bone marrow * Increased destruction of WBCs
160
What are leukemias?
Cancers of the white blood cells or their precursors in the bone marrow.
161
How can leukemias be classified (generally)?
Malignant (cancerous) vs. non-malignant WBC abnormalities
162
Example of a cause of neutrophilia (increased neutrophils)?
Leukemia
163
What are some causes of neutrophilia?
* Infection * Inflammation * Malignancy
164
What is a sign of acute (sudden) or chronic neutrophilia?
Increased presence of band forms (immature neutrophils)
165
What factors can influence the severity of neutrophilia?
* Patient age and health * Invading organism type
166
What is neutropenia?
A condition with a lower than normal white blood cell count specifically for neutrophils (cells that fight bacteria).
167
What are the two main types of neutropenia?
* Acquired (developed later in life) * Inherited (present from birth)
168
What can cause acquired neutropenia?
* Chemical toxicity (e.g., from medications) * Bone marrow problems (e.g., tumors) * Nutritional deficiencies * Increased neutrophil destruction (e.g., from infections) * Neutrophil sequestration (cells trapped in organs like the spleen)
169
What causes inherited neutropenia?
Very rare genetic defects in stem cell development
170
What is an example of a malignant cause of neutropenia?
Mutations or chromosomal abnormalities in leukemias (e.g., chronic myelogenous leukemia)
171
What causes eosinophilia? (High eosinophils)
* Inherited (very rare) * Reactive (caused by allergic reactions, parasitic infections) * Malignant (leukemia)
172
What causes eosinopenia? (Low eosinophils)
* May be difficult to detect due to low baseline levels * Associated with ACTH administration (if adrenal function is normal)
173
What causes basophilia (High basophils)
Hypersensitivity reactions
174
What causes basopenia? (Low basophils)
* Stress * Hyperthyroidism * Increased glucocorticoids
175
What are platelets?
Platelet = fragment of cytoplasm from megakaryocytes (bone marrow cells). Not true cells themselves.
176
Size and resting shape of platelets?
2-3 micrometers, lens-shaped (inactive).
177
What happens to platelets during blood vessel injury?
* Become round and develop projections. * Stick to injured area (endothelial cells/collagen fibers). * Change shape to facilitate clumping (platelet aggregation).
178
What is the function of platelet aggregation?
Form a multi-layered plug to stop bleeding.
179
Where are platelets produced?
Bone marrow, from megakaryocytes (each makes 1,000-3,000 platelets).
180
What do platelet granules contain?
Components affecting the shape and behavior of other platelets and cells during bleeding.
181
How is platelet production regulated?
By thrombopoietin (produced by the liver).
182
What is thrombocytopenia?
Low platelet count.
183
How can thrombocytopenia be treated (sometimes)?
Synthetic thrombopoietin to stimulate platelet production.
184
Typical lifespan of a platelet?
Around 10 days.
185
What does mean platelet volume (MPV) measure?
Average size of platelets in a blood sample.
186
What can an increased presence of large platelets suggest?
* Premature platelet death. * Bone marrow compensating by making more platelets.
187
Why can transfused red blood cells cause an immune reaction?
The recipient's immune system may recognize donor red blood cells as foreign.
188
How does blood grouping prevent transfusion reactions?
Blood groups identify compatible blood types to avoid immune attack on transfused cells.
189
What are the most common blood groups?
A, B, AB, and O
190
What antibodies are present in type A blood?
Anti-B antibodies
191
What can happen if type A blood receives type B blood?
Anti-B antibodies in type A blood attack type B transfused red blood cells.
192
What is special about type O blood?
* Has anti-A and anti-B antibodies. * Can be transfused to anyone (universal donor). * Does not have A or B antigens on red blood cells.
193
Who can receive type AB blood?
Anyone (universal recipient) due to the absence of anti-A and anti-B antibodies.
194
Who can donate blood to someone with type AB blood?
Anyone (A, B, AB, or O) because type AB blood has both A and B antigens.
195
What is the Rh blood group system?
Another important blood group system besides ABO.
196
What is the most important Rh antigen?
Rh(D)
197
Rh positive vs. Rh negative:
* Rh positive: Has Rh(D) antigen on red blood cells. * Rh negative: Does not have Rh(D) antigen.
198
Example: Blood type A negative
A group antigens present, but Rh(D) antigen absent.
