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L.3 Erythropoiesis Flashcards

1
Q

What percentage of body weight does blood constitute?

A

7-8%

This percentage can vary slightly based on factors like body composition and hydration.

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2
Q

What is the approximate blood volume in a 70 kg man?

A

5.6L

Blood volume can differ based on body weight and composition.

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3
Q

What is the composition of blood in terms of solids and water?

A

22% solids, 78% water

The solid components include various cells and proteins.

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4
Q

What is the normal temperature of blood?

A

38°C

This temperature can fluctuate slightly based on the body’s metabolic state.

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5
Q

What is the pH range of blood?

A

7.35-7.4

This slightly alkaline pH is crucial for various biochemical processes.

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6
Q

What are the primary functions of blood?

A

Carries oxygen, water, electrolytes, hormones, vitamins, antibodies, heat TO the body tissues; Carries waste matter (urea), carbon dioxide AWAY from the tissues.

These functions are vital for maintaining homeostasis.

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7
Q

What percentage of blood is plasma?

A

55%

Plasma is the liquid component of blood that contains various dissolved substances.

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8
Q

What percentage of blood is formed elements?

A

45%

Formed elements include red blood cells, white blood cells, and platelets.

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9
Q

What are the main components of formed elements in blood?

A

Red cells (erythrocytes) 99%, Platelets < 1%, Leucocytes < 1%

Erythrocytes are responsible for oxygen transport, while leucocytes are involved in immune response.

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10
Q

What is the structure of a mature red blood cell?

A

Biconcave disc structure

This structure enhances the diffusion of gases.

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11
Q

What is the diameter of red blood cells?

A

7-8 micrometers (μM)

The small size helps in the rapid diffusion of oxygen.

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12
Q

What cellular components do mature RBCs lack?

A

Nuclei, mitochondria, or other organelles

This allows them to be packed full of hemoglobin, maximizing oxygen transport.

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13
Q

What is the normal survival duration of red blood cells?

A

Approximately 120 days

Survival is influenced by the integrity of the red cell membrane and hemoglobin structure.

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14
Q

What happens to senescent red blood cells?

A

They are removed by macrophages

This process is part of the body’s way to recycle components and maintain healthy blood levels.

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15
Q

What are the components of hemoglobin that are recycled?

A

Globin (amino acids reutilized), Iron (reutilized), Hem (excreted in bile)

Recycling helps the body conserve resources and maintain iron levels.

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16
Q

What enzyme do RBCs contain that is crucial for gaseous exchange?

A

Carbonic anhydrase

This enzyme catalyzes the conversion of CO2 and H2O into bicarbonate.

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17
Q

What stable molecule is created by the action of carbonic anhydrase?

A

Bicarbonate (HCO3-)

Bicarbonate is formed from CO2 and H2O.

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18
Q

How does HCO3- compare to CO2 in terms of solubility in plasma?

A

HCO3- dissolves much better than CO2

This allows for greater transportation of carbon dioxide in the blood.

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19
Q

What is the significance of HCO3- in blood?

A

It acts as an important buffer, maintaining a stable pH of about 7.4

This pH level is optimal for cellular functions.

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20
Q

Why is maintaining a stable pH in blood important?

A

It creates an environment where cellular machinery works best

Optimal pH is crucial for enzyme activity and overall cellular health.

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21
Q

What happens to HCO3- when it arrives in the capillaries of the lungs?

A

It is converted back to gaseous CO2 by RBCs and then diffuses out into the lungs to be breathed out.

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22
Q

At what average rate are erythrocytes replaced?

A

2-3 million cells/second.

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23
Q

What was the original belief about the role of BM macrophages in erythropoiesis?

A

They were thought to be present simply to scavenge and phagocytose extruded nuclei.

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24
Q

What is the current understanding of the role of macrophages in erythropoiesis?

A

They provide cytokines and other signals crucial for the promotion of erythropoiesis.

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25
How do macrophages promote the maturation and proliferation of proerythroblasts and erythroblasts?
Through close physical proximity and characteristic cytoplasmic protrusions.
26
What facilitates the close proximity between macrophages and erythroblasts?
The interaction of adhesion molecules on both cell types.
27
What happens to erythroblastic islands as erythroid maturation proceeds?
They migrate to regions of the BM (the sinusoids) close to blood vessels.
28
What is the purpose of erythroblastic islands migrating to the sinusoids?
To facilitate the migration of reticulocytes and erythrocytes into circulation.
29
What is the role of macrophages in the bone marrow regarding erythroid progenitors?
Macrophages provide signals that induce differentiation and proliferation of the earliest committed erythroid progenitors. ## Footnote This process is crucial for the development of red blood cells.
30
What are erythroblastic islands?
Erythroblastic islands are structures in the bone marrow where a central macrophage provides cues to induce erythroblast differentiation, expansion, and haemoglobinisation. ## Footnote These islands are essential for the maturation of erythrocytes.
31
What happens to erythroblasts during maturation?
Erythroblasts extrude their nuclei, which are then phagocytosed by macrophages, while reticulocytes are released into circulation. ## Footnote This process marks the transition from erythroblast to mature red blood cell.
32
What are reticulocytes?
Reticulocytes are early erythroblasts that contain remnants of ribosomal RNA. ## Footnote They can be identified by their reaction with certain dyes, indicating their status in erythropoiesis.
33
What dye reacts with ribosomal RNA in reticulocytes?
New methylene blue produces a blue precipitate when reacting with rRNA. ## Footnote This characteristic is used for identifying reticulocytes in laboratory settings.
34
Which flow cytometry dyes bind RNA?
Auramine O and Thiazole Orange both bind RNA. ## Footnote These dyes are used to assess erythroid precursors in bone marrow biopsies.
35
What is the normal percentage count of reticulocytes?
0.2 - 2.0% ## Footnote It is important to report the absolute count of reticulocytes for accurate assessment.
36
What conditions can lead to high reticulocyte counts?
* Bleeding * High altitude * Haemolytic anaemia * Babies ## Footnote High reticulocyte counts indicate increased red blood cell production in response to various stimuli.
37
What conditions can lead to low reticulocyte counts?
* Aplastic anaemia * Iron deficiency anaemia * Radiation ## Footnote Low reticulocyte counts suggest decreased red blood cell production.
38
What is erythropoiesis controlled by?
GFs such as SCF and EPO
39
Where is erythropoietin (EPO) produced?
90% in the kidney and 10% in the liver
40
What is the primary action of EPO on the BFU-E?
Promotes cell division and differentiation
41
What pathway is activated upon EPO receptor (EpoR) engagement?
JAK2 pathway
42
What activates the production of EPO?
Tissue hypoxia
43
What happens to EPO levels when sufficient oxygen is restored?
EPO can be reduced
44
What is a consequence of constitutive activation of the JAK2 pathway due to EPO?
Myeloproliferative neoplasm
45
What does EPO induce that leads to signalling termination?
EpoR endocytosis
46
What can defects in EpoR endocytosis lead to?
Congenital polycythaemia
47
List the cells that EPO acts on to promote cell division and differentiation into normoblasts.
* CFU-GEMM * BFU-E * CFU-E * Pro-Normoblast * Basophilic Normoblast
48
What effects does EPO have on dividing cells?
* Shorten the cell cycle time * Shorten the maturation time * Inhibit apoptosis * Promote reticulocyte release from the bone marrow
49
What staining method demonstrates reticulocyte RNA and Heinz bodies?
Supravital staining (New Methylene Blue) ## Footnote This method is used to visualize specific cellular components that are not visible with standard staining techniques.
50
What are Heinz bodies?
Oxidised denatured Hb ## Footnote Heinz bodies are indicative of oxidative stress and hemolytic anemia.
51
What do siderotic granules contain, and how do they appear with different stains?
Contain iron; purple with conventional staining, blue with Perls stain ## Footnote Siderotic granules are associated with iron metabolism and can indicate certain types of anemia.
52
What is a Howell-Jolly body?
A DNA remnant ## Footnote Howell-Jolly bodies are typically seen in conditions where splenic function is compromised.
53
What does basophilic stippling represent?
Denatured RNA ## Footnote Basophilic stippling can be associated with lead poisoning and certain types of anemia.
54
What does MCV stand for, and what does it indicate?
Mean Corpuscular Volume; average volume of the red cell (fL) ## Footnote MCV helps classify anemia as normocytic, microcytic, or macrocytic.
55
What does MCH represent?
Mean Corpuscular Hemoglobin; average weight of Hb in the red cell (pg) ## Footnote MCH is used to classify red blood cells as normochromic or hypochromic.
56
What is MCHC?
Mean Corpuscular Hemoglobin Concentration; average concentration of Hb in RBC volume (g/L) ## Footnote MCHC provides insight into the hemoglobin saturation of red blood cells.
57
What happens to RBCs while in circulation?
They slowly accumulate damage that is repaired by macrophages of the spleen ## Footnote This process is essential for maintaining RBC integrity and function.
58
Why can't RBCs generate new enzyme molecules?
They have no DNA or ribosomes ## Footnote This limitation leads to the depletion of essential enzymes such as G6PD and pyruvate kinase.
59
How long do RBCs typically circulate before being removed?
120 days ## Footnote After this period, senescent RBCs are removed by macrophages in the spleen and liver.
60
What is the primary site of RBC recycling?
Extravascular, 90% of recycling occurs here ## Footnote Intravascular recycling accounts for only 10%.
61
What is the difference between extravascular and intravascular hemolysis?
Extravascular: RBC destruction in spleen or liver; Intravascular: RBC destruction within the circulation ## Footnote Understanding these processes is crucial for diagnosing hemolytic anemias.
62
What happens to the hemoglobin molecule during hemolysis?
It is degraded, and proteins, lipids, and iron are recycled ## Footnote This recycling is vital for maintaining iron homeostasis in the body.
63
What is produced from the protoporphyrin ring during degradation?
Iron (ferritin > hemosiderin, transferrin), carbon monoxide, and biliverdin (> bilirubin) ## Footnote This process is facilitated by the enzyme haemoxygenase.

Haematology (20 decks)

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