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IMED2002 > Erythropoeisis > Flashcards

Erythropoeisis Flashcards

1
Q

What is blood?

A

Suspension of cells in water, proteins and electrolytes (plasma)

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2
Q

Average volume of blood

A

5 L

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3
Q

Plasma contains…

A

Coagulation proteins (clotting factors)

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4
Q

cellular component of blood

A

leucocytes, platelets (buffy coat)

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5
Q

erythrocytes make up the

A

the haematocrit

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6
Q

Where are cells made

A

in the bone marrow

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7
Q

When blood is centrifuges, where to RBCs go

A

they sediment to the bottom of the tube

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8
Q

What is haemopoiesis?

A

the process of blood cell production in the bone marrow (BM)

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9
Q

Which cell is the most primitive in the BM

A

Pluripotent stem cell (HSC)

they differentiate to form all types of blood cells

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10
Q

What is the haemopoiesis of HSC influenced by?

A

Cytokines

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11
Q

The HSC has 2 characteristics that allow it to divide and differentiate - what are they?

A

Self-renewal (capacity to replicate itself)

Pluripotent (ability to differentiate along all cell lines and make all types of blood cells)

One progeny committed to a particular lineage, matures and differentiates
it is a committed precursor cell

These are CD34 + cells

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12
Q

The pluripotent immature HSC can divide into 2 types of stem cells - these are:

A

The myeloid stem cells and the lymphoid stem cells

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13
Q

The myeloid stem cells develop into, which develop into…

A

progenitor cells, which develop into blast cells

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14
Q

The lymphoid stem cells develop into

A

Blast cell (lymphoblast)

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15
Q

What types of myeloid blast cells are there?

A

Proerythroblast
Myeloblast
Monoblast

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16
Q

Do platelets have a blast cell progenitor?

A

No , only the megakaryocyte

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17
Q

What is the differentiation process of the proerythroblast?

Describe the process by which red blood cells are produced (erythropoiesis)

A 
It becomes basophilic erythroblast (blue) 
Then polychromatic erythroblast 
Then orthochromatic erythroblast 
Then a reticulocyte 
And then an erythrocyte

The cell gets smaller and the nucleus also gets smaller,
the nuclear chromosomes condense and shrink
The color changes as the RBC acquires Hb
The nucleus is extruded out of the cell in the end
The RBC mends the defect in the membrane and then the cell is anuclear, mature and can circulate

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18
Q

What is the differentiation process of the myeloblasts

A

They differentiate into myelocytes
Then band cells
and then the individual basophil, eosinophil, neutrophil

which all 3 make the granulocytes (WBCs)

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19
Q

What does the monoblast differentiate into?

A

Promonocyte, and then the monocyte

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20
Q

What does the lymphoblast differentiate into

A

The prolymphocyte and then the lymphocyte

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21
Q

Which cells are the leukocytes

A

Basophil, eosinophil, neutrophil, monocyte, lymphocyte

Monocyte & lymphocytes are agranulocytes
Whilst the rest are granulocytes

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22
Q

Where is the blood made?

A

Made in the BM

In utero - foetus makes blood cells in the yolk sac at about 6 weeks (yolk sack is an embryonic organ that no longer functions and regresses later on)

Yolk sac haemopoeisis declines over time and the liver and spleen begin to be the major blood producing organs in the foetal body but then they also decline (but don’t completely disappear from blood production capability) ​

At about 4 months of foetal age, the BM starts to work and becomes the major blood forming organ in our body throughout life​

​The BM haemopoiesis activity in the long bones like the tibia and the femur decline at about 20-25 years of age

But the ribs, sternum, vertebra continue their hemopoietic activities (mostly the vertebra)

​

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23
Q

Where is blood made in the BM

A

In the hard bony cavity

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24
Q

Is the BM an organ?

A

The bone marrow is the most rapidly replicating organ in the body which makes blood cells throughout our life

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25
Q

HSC differentiation in the BM needs:

And what does the BM stroma have?

A

BM needs cytokines, regulators, metals, vitamins

Stroma contains Blood vessels, fat and bone

26
Q

Mature blood cells are …

talk about how long the cells live for

A

Mature blood cells don’t proliferate, they go into the circulation and then they die

Don’t live forever, only for some time and then naturally die (deciduous)

RBCs made everyday with 120 day lifespan

Platelets survive for 10 days

Granulocytes only spend hours in the blood

BM is constant source of blood cells, because of the short lifespan of the dying cells & the need for replacement

27
Q

What is BM failure?

A

Inadequate blood production

28
Q

Normal BM color

A

red

29
Q

Non-functional BM color

A

Yellow

30
Q

What is the process of granulopoeisis

A

Myeloblast > Promyelocyte > Myelocyte > Metamyelocyte > band form > neutrophil

31
Q

What is aspirated of bone marrow

A

Take a bone marrow sample using a syringe & then can then identify individual cell types​

Take a sample of bone marrow from the posterior, superior iliac crest (or from a child’s anterior tibia)​

32
Q

Bone marrow biopsy

A

pink structures in the biopsy are thin shards of trabecular bone

pink and blue are BM cells

the white spaces are fat spaces, which we all have in our BM, and in fact the fat content increases with age

33
Q

How is haemopoiesis regulated

A

By growth factors like cytokines​ which are cell hormones:​

Control differentiation of haemopoietic stem cells​

Control the number of cells being produced in the bone marrow​

Can affect the function of a cell​

Cytokines regulate which, how many, & at what rate are blood cells made (controlled by cytokines)​

If there is a deficiency of one particular cell type, the cytokine will control differentiation of haemopoietic stem cells to make up for that​
(Drives the HSC to drive the production of the deficient cell type)

34
Q

Difference between the different types of cytokines / growth factors:​

A

Some act on primitive cells only​

Some act on later cells committed to a particular cell lineage​

35
Q

Examples of cytokines in the bone marrow that work on later cells, committed to a particular cell lineage

A

EPO: works on RBC
Erythropoietin is a specific cytokine that drives the pluripotent stem cell down the differentiation pathway to make more RBCs (EPO) – drives erythropoiesis​

G-CSF: works on granulocytes
Granulocyte colony stimulating factor is a cytokine that drives granulocyte production (G-CSF) used for patients deficient in granulocytes and are getting infections ​

36
Q

Example of a cytokine that has broad specificity and works on pluripotent stem cells

A

IL3

37
Q

Where is EPO made?? what does it do?

A

In the kidney, it is reduced during kidney failure

Increases RBC production

38
Q

How do we assess haemopoiesis?

A

Blood count, BM examination, cytokine measurement

39
Q

Blood count

A

Venous blood used
Anti-coagulated
Sample goes to lab to be tested and analysed

40
Q

Blood film - what does it tell us?

A

morphological appearance, whether cells look normal

Number and morphology

41
Q

Erythrocytes

A

small, flexible, biconcave disc shape
lipid & protein RBC
blood groups on RBC membrane (proteins carry them)

carry Hb to tissues - Hb present in cytoplasm

Need a flexible & deformable membrane to pass through the microcirculation

Nucleus is rock hard (hinderance)

To make RBC, require iron, folate, vit B12, and EPO

lifespan: 120 days

42
Q

What does Epo do

A

Pluripotent stem cell under influence of EPO undergoes maturation to generate mature circulating RBCs from proerythroblasts (which are large early cells)

43
Q

Where does erythropoeisis occur

A

Next to macrophages, which have storage iron in them (ferritin), that they deliver to the developing RBC so that the RBC can make haeme for Hb

Macrophages nurse the proerythroblasts, delivering them iron so they can fully mature

44
Q

Stimulus to EPO production is

A

renal O2 tension like:

Anaemia –> hypoxia , low atmospheric O2, defective cardiac or pulmonary function stimulate erythropoiesis​

45
Q

How much EPO produced in kidney

A

90% produced in kidney

46
Q

EPO travels from where to where?

A

EPO goes from the kidneys to the BM to drive erythropoeisis

47
Q

EPO drive accelerates & increases production of new red blood cells from their progenitors
true or false

A

true

3-4 days is the duration it takes to make RBCs, can be increased in amount and reduced in time (to make RBC)​

48
Q

Chronic renal failure = cause for anaemia

true or false

A

True

Chronic renal failure means the person can no longer make EPO - and the patient will become anaemic ​

49
Q

Hb structure:

A

Haem attached to 4 globin chains
Haem is responsible for transporting oxygen
there are 4 subunits, each containing iron

50
Q

Where is haem made? What if not made properly?

what does haem contain

A

In the mitochondria
anaemia
Iron

51
Q

What are the globin chains like?

A

4 polypeptide chains

HbA: alpha2beta2 (98%)

52
Q

Haemoglobin and Oxygen Transport​

A

Hb loaded with O2 as RBC pass through pulmonary capillaries in lungs​

Hb-bound O2 transported to tissues via circulating red cells and then released​

53
Q

“Oxygen-Haemoglobin Dissociation Curve“

A

“Oxygen-Haemoglobin Dissociation Curve“ determines unloading and based on partial pressure of O2 oxygen​

Alterations in tissue O2 delivery in response to decreased O2 supply (high altitude) or increased demand (hypoxia; cardiovascular disease)​

54
Q

Iron travel

A

Iron transported to marrow, bound to transferrin
Transferrin will deliver the iron through transferrin receptors on the developing RBC in the bone marrow​

​

55
Q

List all of the qualities of RBCs

A

RBC do not have a nucleus and cannot reproduce​

RBC contain no cell organelles (i.e. no mitochondria, golgi, endoplasmic reticulum or lysosomes)​

RBC have no synthetic activities (no protein biosynthesis, lipid synthesis or carbohydrate synthesis)​

RBC must be able to squeeze through some tight spots in microcirculation​

RBC must be easily and reversibly deformable​

RBC must make their own energy​

56
Q

Normal RBC morphology

A

Biconcave shape with central pallor​

57
Q

Globin chains of Hb

A

Two pairs of globin chains comprise Hb​

alpha globin chains:​
Two α genes on each chromosome 16​
Each responsible for 25% of normal total α chain synthesis​

non-alpha globin chains:​
one β gene on each chromosome 11​
β gene part of complex containing delta & gamma genes​

58
Q

Red Blood Cell Metabolism​ & generation of ATP

A

RBC use none of the O2 they transport​

RBC produce the energy carrier ATP​

Glucose metabolised by anaerobic glycolysis​

(requires no mitochondria & no O2)​

Embden-Meyerhof pathway​

One molecule of glucose yields 2​ molecules of ATP​

ATP is required to maintain RBC shape and energy for deformability​

Two molecules of lactate are produced​

Lactate is transported to blood and in the liver converted to glucose​

59
Q

RBC membrane & cytoplasm contains

A

Membrane: phospholipid membrane with proteins​

Cytoplasm: red cells contain haemoglobin (Hb)​

transports O2 from lungs to tissues​

returns CO2 to lungs​

60
Q

Describe the process by which red blood cells are produced (erythropoiesis)

A

Under influence of EPO​

Stages of development:​
Large early cells (erythroblast)​
Cells get smaller as they mature​
Nucleus: chromatin condensation​
Haemoglobin in cytoplasm​
Nucleus extruded​

Islands near macrophages​
Mature red blood cells​
Anuclear biconcave disc​
Flexible cell membrane​

IMED2002 (12 decks)

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