8/12/2019 [MICROA - 2.1] Myeloid Tissue Histology

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

Outline:

Review of bone and BM histology

Erythropoiesis

Granulopoeisis

Platelet formation

Clinical Correlation

REVIEW OF BONE

FUNCTION OF BONE

Support for soft tissues and the attachment site

for tendons.

Because the bone is very hard, It protects the

soft internal organs like your brain. It is

protected from the external environment by the

very hard skull.

In combination with the muscle, it is responsible

for locomotion.

The bone also has a biochemical function. It

stores mineral (e.g. calcium and phosphates)and

is released whenever theres a need for them.

Blood cell production. It also has another

biological function, which is to produce the cells

that are found in the blood.

Triglyceride storage. It stores triglyceride in the

form of yellow marrow.

Explanation: This is a cross-section of a bone showing you

two types. The one in the surface is the CORTICAL

(Compact) BONE. So if its enlarged, you can see that its

made up of units known as OSTEON and in the center,

you will find the HAVERSIAN CANAL and the ones

concentrically arranged around it are the OSTECYTES.

Pointed above is the TRABECULAR (Spongy) BONE. The

trabecular bone itself is not in the picture but its actually

the marrow which fills the spaces within the trabecular

bone.

HISTOLOGY OF BONE MARROW

TYPES OF BONE MARROW (OVERVIEW)

Red Marrow Actively involved in

hematopoeisis.

o

Contents: Stem Cells, Progenitor Cells

Developing Erythroblasts, Myeloblasts

and Megakaryoblasts.o Highly cellular. The spaces are filled with

actively dividing hematopoietic cells.

Yellow Marrow storage site for adipocytes.

o

Contents: Adipose cells (varies with age

and activity)

Note: Both marrows contain a lot of dilated capillaries

Theres a wide network of capillaries present in the

marrow.

YELLOW MARROW

Located on long bonesof adults. (e.g. femur)

Highly infiltrated with

fat.

Not hematopoietic

under normal

conditions. But it has a

potential to become when theres a need fo

extra hematopoietic cell.

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8/12/2019 [MICROA - 2.1] Myeloid Tissue Histology

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

Explanation: This is how it looks like under a microscope.

The yellow marrow is composed of spaces between

trabecular bones and is filled with several adipose cells.

The adipose cells are filled with triglycerides.

RED MARROW

Located in the epiphysis of long bones, flat,

irregular, and short bones. (e.g. Sternum)

Highly vascular with large dilated venous sinuses

and surrounding them are the active

hematopoietic cells.

Explanation: The red marrow is filled with several venous

sinuses, arising from an artery. The green-colored objects

are the RETICULAR FIBERS, which provides support to the

hematopoietic cells.

Explanation: The clusters of solid blue cells are the

ERYTHROPOIETIC CELLS. The clusters of granulated blue

cells are the GRANULOPOIETIC CELLS. The white space

filled with RBCs is the VENOUS SINUS. It is normal to find

adipose cells. The distribution for adults is 50%

hematopoietic cells and the remaining 50% are adipose

cells.

Explanation: There is a prominent VENOUS SINUS filled

with RBCs. Surrounding them will be the

HEMATOPOIETIC CELLS, specifically ERYTHROPOIETIC

CELLS. A large cell is also present here known as the

MEGAKARYOCYTE.

Amount of red marrow varies according to the

patients age.

o

Childhood:

Virtually present in all bones o

the body.

It is composed of hematopoietic

cells. Virtually no adipose cells

are found.

o

Adults:

Reduced to 50%

Present in the sternum, ribs

pelvis and skull.

o 70 years:

Reduced to 30%

ERYTHROPOIESIS

Pluripotent Stem Cell Blast Cells Proerythroblast

Basophilic Erythroblast Polychromatic Erythroblast

Orthochromatic Erythroblast Reticulocyte

Erythrocyte

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

HOW DO WE DISTINGUISH ERYTHROPOIETIC CELLS?

FROM OTHER HEMATOPOIETIC CELLS

o As a group, they do not have any

prominent granules in contrast to the

developing myelocytes.

o

The nucleus, whether small or large, is

consistently round when its still present.

In contrast to the developing WBCs

where the shape of the nucleus varies

according to stage of its development.

FROM EACH STAGE

o

Cell sizeo Subtle differences in the nucleus

o Color of the cytoplasm

TREND IN THE DEVELOPMENT OF RBCs

Explanation: If the cell develops from young to mature,

youll notice a change in the nucleus. Initially, it is big it

becomes smaller until eventually disappears. There is a

PROGRESSIVE CONDENSATION of the nucleus.

Another trend is that there is a change from Basophilic to

Eosinophilic. Initially, there is no haemoglobin. But

eventually, an accumulation of haemoglobin will be

present as the cell progress thereby giving it its

eosinophilic quality. Since there is absence ofhaemoglobin during the early stage of erythropoiesis,

there is a production of RNA present. These RNA will

contribute to the production of RIBOSOMES. This gives

the cell its basophilic characteristics. The RNA and

ribosome are the ones involved in protein synthesis,

namely haemoglobin.

There is also a progressive reduction in the size of the

cell. It initially starts with a large cell and as it matures,

the cell is now smaller.

STAGES OF ERYTHROPOIESIS

BLAST CELL

o The origin of erythropoietic cells.

o Cannot be distinguished from the blas

cells of myelocytes series.

o

Mitotically active (It divides).

o No granules.

PROERYTHROBLAST

o

Cell is large.

o Mitotic.

o Positive nucleoli (w/c means that its

actively involved in synthesis of RNA).o Basophilic cytoplasm.

BASOPHILIC ERYTHROBLAST

o

The nucleolus has disappeared (w/c

means the synthesis of RNA has

stopped).

o

Intensely basophilic because o

ribosomes.

POLYCHROMATIC ERYTHROBLAST

o

Smaller than its precursor.o The nucleus is starting to condense

thats why it has a checkerboard

appearance (Writes stain).

o

Gray-green cytoplasm because o

haemoglobin accumulation.

ORTHOCHROMATIC ERYTHROBLAST

o Aka Normoblast

o Smaller pyknotic nucleus (about to be

extruded)

o

Pink cytoplasm due to haemoglobin

accumulation.

RETICULOCYTE

o No nucleus (already extruded)

o Pink/orange color (because of the

haemoglobin) with bluish hue (due to

remaining ribosomes).

o

Named such because of cresyl blue

They seem to have a network-like

appearance.

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

IN SUMMARY:

Decrease in basophilia

Increase in haemoglobin concentration

Decrease in cell volume

Increase in chromatin condensation, followed by

extrusion of a pyknotic nucleus

GRANULOPOIESIS

All granulocytes arise from a single MYELOBLAST which

came from a UNIPOTENT STEM CELL. The development of

all types of myelocytes follows the same stages.

HOW DO WE DISTINGUISH GRANULOPOIETIC CELLS?

FROM OTHER HEMATOPOIETIC CELLS

o

Consistently contain granules

o

When clustered as a group, they appear

DIRTY together.

FROM EACH STAGES

o Type of granule present

o Appearance of the nucleus

STAGES OF GRANULOPOIESIS

PROMYELOCYTE

o

First identifiable WBC precursor.

o Contains purple-staining azurophilic

nonspecific granules.

o Cell is large.

o

Nucleus is large.

o Nucleolus is prominent.

MYELOCYTE

o

Distinguished once the lilac-staining

specific granules start appearing ove

the purple-staining azurophilic

nonspecific granules.o Wide range in cell size.

o Frequently indented round nucleus.

METAMYELOCYTE

o The primary granules will start to

disappear and the secondary granules

will predominate.

o Nucleus becomes flattened.

BAND

o

The nucleus will become morecondensed. Eventually, it will become

U-shaped or horseshoe-shaped.

GRANULOCYTE

o The nucleus becomes segmented into

lobes.

IN SUMMARY:

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

Myeloblast = No cytoplasmic granules

Promyelocyte = appearance of Primary Granules

Myelocyte = appearance of Secondary granules

Metamyelocyte = Abundance of Secondary

granules and dispersed Primary Granules

Band = Nucleus will become horseshoe-shaped

Granulocyte = Nucleus is segmented

PLATELET FORMATION

OVERVIEW: Consist of 3 stages and it arose from the

Unipotent Stem Cell. It will divide to form the

MEGAKARYOBLAST. The megakaryoblast will undergo

ENDOMITOSIS to form MEGAKARYOCYTE. And the

megakaryocyte will fragment to form the platelet.

STAGES OF PLATELET FORMATION

MEGAKARYOBLAST

o

Large cell with single large-lobed

nucleus.

o Basophilic non-granular cytoplasm.

o

It will undergo ENDOMITOSIS (nucleusis doubled up but doesnt undergo

division).

o RARE

MEGAKARYOCYTE

o Extremely large cell with single, large

POLYPLOID nucleus.

o

Lies just outside the sinusoids.

o Fragments to platelets.

o Sheds platelets.

o

They are found near the sinusoidsbecause they form PSEUDOPODS that

fragments to form platelets goes

directly to the sinusoids to join the

bloodstream or circulation right away.

CLINICAL CORRELATION

ACUTE MYELOGENOUS LEUKEMIA

LEUKEMIA the uncontrolled proliferation of the

myelocyte.

ACUTE MYELOGENOUS LEUKEMIA the uncontrolled

proliferation of UNDIFFERENTIATED MYELOBLAST.

COMPARISON:

Bone Marrow w/ AML

o

Highly cellular

o

Everythings obliteratedo Absence of erythropoietic cells

o Abundance of myeloblastic cells

o

Absence of fats

o Absence of platelet forming cells

o

Obliteration of marrow space with tumor

cells

SYMPTOMS (Purely based on the slides):

Increased WBC

o

Caused by the abundance in myeloblast

but are immature and non-functional.

Infection

o WBCs are non-functional

Anemia

o

Obliteration of erythropoietic cells

Bleeding

o

Obliteration of platelet forming cells

Pain

o

Since it is growing in the confined space

of the bone

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2.1 MYELOID TISSUE HISTOLOGY

LECTURER: Dennis Ivan U. Bravo, MD

DATE: 15 July 2014FEU-NRMF Institute of Medicine

Batch 2018

John Henry Caas, ECT

07-20-14

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