Erythropoiesis (RBC Maturation)

What are the stages of normoblastic maturation, in order?

1. Multipotential stem cell

2. Pronormoblast

3. Basophilic normoblast

4. Polychromatophilic normoblast

5. Orthochromic normoblast

6. Reticulocyte

7. Erythrocyte

Once the ______ stage is reached, division stops.

orthochromic normoblast

As an RBC matures, what aspects become smaller?

Cell size, nuclear size

What is this due to?

"Loss" of nucleoli, condensation of chromatin, possible shape change and/or ejection

As an RBC matures, nucleoli ______.

disappear

As an RBC matures, the nuclear chromatin pattern becomes more ______.

condensed

As an RBC matures, the cytoplasm turns from a ______ color to ______.

blue, red

This is due to a decrease in ______ and an increase in the amount of ______.

basophilia, cytoplasm

In a blue-stained RBC stage, the ______ components of the cell attract the ______ stain (blue).

acid, basic

The blue color of the cytoplasm is due to a higher amount of ______.

rRNA

In a pink-stained RBC stage, the ______ components of the cell attract the ______ stain (pink).

basic, acid

When an RBC appears pink, there is an accumulation of ______.

Hgb

A pink RBC is known as ______.

eosinophilia/acidophilia

What is the N:C ratio?

The nuclear:cytoplasmic size ratio

The entire RBC maturation process takes ______ days.

7-8

A mature RBC is ~______um in diameter.

6

1. Pronormoblasts are about ______ times the size of an RBC.

2-3

Pronormoblasts have the largest ______.

nucleus (N:C ratio)

Pronormoblasts have 1-2 ______ that are slightly lighter in color.

nucleoli

Pronormoblast cytoplasm is very ______ and ______ along the outside.

blue, irregular

Pronormoblast mitosis can occur ______ time(s).

>1

The pronormoblast stage lasts ______.

~24 hours

Pronormoblast

2. Basophilic normoblasts are slightly ______ than pronormoblasts.

smaller

Basophilic normoblasts have a smaller ______ than pronormoblasts.

nucleus (N:C ratio)

The basophilic normoblast cytoplasm is deeper, richer ______ than pronormoblasts.

blue

Basophilic normoblast stage lasts ______.

~24 hours

Both pronormoblasts and basophilic normoblasts are found in the ______.

bone marrow

Basophilic normoblast

All RBC stages after this point are found in the ______.

peripheral blood

3. Polychromatophilic normoblasts are around the same size/slightly smaller than ______.

basophilic normoblasts

The nuclear size of polychromatophilic normoblasts can vary from ______ to ______.

4:1, 1:1

Polychromatophilic normoblasts do not have ______ present.

nucleoli

Polychromatophilic normoblasts cytoplasm is varying color, trending into ______.

pink

Polychromatophilic normoblasts are the last stage to undergo ______.

mitosis

How many mitotic divisions do basophilic and polychromatophilic normoblasts undergo?

1

Polychromatophilic normoblast

4. Orthochromatophilic normoblasts are ______ than the three previous RBC stages.

smaller

The N:C ratio of orthochromatophilic normoblasts is ______.

1:1

The orthochromatophilic normoblast nucleus is ______ and ______ at the end of the stage.

pyknotic, extruded

The orthochromatophilic normoblast cytoplasm is what color?

Pinkish/red with a slight bluish hue

Orthochromatophilic normoblast

5. Reticulocytes are the same size as ______.

orthochromatophilic normoblasts

Reticulocytes are also called ______.

polychromatic erythrocytes

Reticulocytes have no ______.

nucleus

Reticulocytes can be stained with what stains?

Wright and supravital/New Methylene Blue

Wright stain produces reticulocytes with ______.

polychromasia (pink/blue/purple)

Supravital stain/New Methylene Blue stains aggregated ______ what color?

RNA, blue

Reticulocyte

Wright stain

Reticulocyte

New Methylene Blue

The reticulocyte goes from the blood to the ______.

spleen

What occurs here?

The reticulocyte is "polished" by macrophages, giving the biconcave discoid shape of a mature RBC

A mature erythrocyte has a surface:volume ratio that enables for optimal ______.

gaseous exchange

The function of erythrocytes is to deliver ______.

oxygen

Erythrocytes live for ______.

120 days

Erythrocyte

The term "erythron" encompasses all stages of ______ throughout the body.

RBCs

RBC mass is the ______ in blood.

circulating RBCs

______ of the kidney sense hypoxia.

Peritubular fibroblasts

This hypoxia causes peritubular fibroblasts to release ______.

erythropoietin (EPO)

EPO release from Peritubular fibroblasts is ______ so there is continuous replacement of dying RBCs.

constant

EPO release is increased during what scenarios?

Hemorrhage, increased RBC destruction, defective Hgb

______ in the liver also produce EPO.

Hepatocytes

EPO is a thermostable, glycoprotein ______.

hormone

EPO has a carbohydrate unit that binds to a receptor on ______.

RBCs

EPO has a sialic acid unit that has ______ activity.

biological

EPO is produced in the ______ and acts at the ______.

kidney, BM

EPO allows early release of ______ from the BM.

reticulocytes

EPO does this my increasing the width of space between the ______ cell layer so RBCs can get through.

adventitial

EPO also downregulates the expression of ______ molecules on RBCs that keep it in the BM.

adhesion

EPO prevents ______ of RBCs.

apoptosis

EPO does this through removing ______ from the surface of RBC precursors.

Fas

When Fas binds to FasL, ______ is induced.

apoptosis

EPO also induces expression of ______ molecules.

anti-apoptotic (Bcl-XL)

EPO reduces time necessary for RBCs to ______ in the BM by 2 days.

mature

EPO does this through increasing synthesis of ______ and ______.

RNA, Hgb

EPO also decreases ______ molecule expression and increases ______-promoting surface molecules to speed up RBC maturation.

adhesion, egress

EPO also stops cell ______ and reduces the time spent between ______.

division, mitoses

RBCs lack a nucleus so it cannot generate new ______.

proteins/enzymes

This causes RBC ______ to decline, eventually causing death.

functions

Since RBCs have no mitochondria, ______ is the only source of ATP.

glycolysis

Loss of glycolytic enzymes = cellular ______ = senescence.

aging

RBCs can also die via _______ in the spleen.

phagocytosis (by macrophages)

Extravascular hemolysis occurs when decreased ATP causes failure of RBC ______.

membrane

What are the consequences of this?

- Oxidation of proteins and lipids

- Inability to pump out Na+

- Loss of selective permeability

- Water enters the cell and it becomes spherical

Spherical RBCs cannot leave the ______.

spleen

When this happens, splenic ______ trapped RBCs.

macrophages phagocytose

This accounts for ______ of RBC loss.

~90%

Intravascular hemolysis occurs when RBCs ______ within blood vessels.

rupture

Stress on the RBC causes ______ of the cell and loss of intracellular contents.

fragmentation

What organs release EPO?

kidneys and liver

What is the order of maturation for hematopoiesis?

Pluripotent, progenitor, precursor

What is the primary site of hematopoiesis in a 4 month fetus?

Liver

An infant's thymus is ______ than an adult's.

larger

CFU-GEMM stem cell cannot become a ______.

lymphocyte

Stromal cells in the BM help to form ______.

extracellular matrix

Leukocytosis

Too many leukocytes

CD34 is expressed on ______ cells.

stem