Lecture 1: Hematopoiesis Flashcards
What is hematopoiesis?
Hematopoiesis is the formation of blood cells in the bone marrow of the [Pelvis, proximal femur, skull, sternum, ribs, vertebrae].
What are all cells derived from?
A single, pluripotent HSC (hematopoetic stem cells).
All cells are derived from a single, pluripotent HCS. What is this theory called?
Monophyletic theory.
What is the monophyletic theory?
The monophyletic theory says that all cells are derived from a single, pluripotent HCS.
HCS will divide into 2 common progenitor cells (common lymphoid progenitor cells and common myeloid progenitor cells).
Common myeloid progenitor cells (CMP) then divide into MEP (megakaryocyte/erythrocyte progenitor cells) and GMP (granulocyte monocyte progenitor cells).
HCS will divide into what?
- CLP (common lymphoid progenitor cells)- directly divide into lymphocytes.
- CMP (common myeloid progenitor cells)
What does CMP divide into?
- Granulocyte/monocyte progenitor cells (GMP)
2. Megakaryocyte/erythrocyte progenitor cells (MEP).
What are the phases of hematopoeisis, at the 1st trimester, 2nd trimester and 7th month?
- Hematopoiesis begins in the fetus in the 1st trimester in the umbilical vesicle (yolk sac).via hemangioblasts (progenitors of hematopoeitic and endothelial cells)
- Continues in the 2nd trimester in the liver (primarily) and spleen.
- During 7th month, the bone marrow becomes the primary site of hematopoiesis.
In the first trimester, where does hematopoiesis begin?
Umbilical cord (vesicle sac).
Where do hematopoietic islands develop from?
Hemangioblasts
What are hemangioblasts?
Hemangioblasts make hematopoietic and endothelial cells.
In the 2nd trimester, where does hematopoiesis continue to occur?
- Liver (primarily)
2. Spleen
During month 7, what becomes the primary site of hematopoeisis?
Bone marrow.
As we age, where do we see an increase in hematopoiesis?
- . Ribs
- . Sternum
- Vertebrae
What is bone marrow and what is it made up of?
Bone marrow is the tissue in bone that makes BC.
It is made up of:
- blood vessels
- hematopoetic cells
- sinusoids
What are sinusoids?
Sinusoids are fenestrated capillaries that are made up of [endothelial cells and adventitial cells] and have a discontinuous basement membrane, making the bone marrow porous.
Sinusoids are a part of bone marrow that separate the [hematopoietic compartment from peripheral circulation].
What are adventitial cells?
Adventitial cells incompletely cover sinusoids. They help to support developing BC by
- making reticular fibers
- secreting cytokines (CSFs, IL-5 and IL-7].
What lies in between sinusoids?
Hematopoietic cords
What type of system is the [bone marrow-sinusoid system]?
A closed system where newly made BC must escape the sinusoid by penetrating the endothelium so that it can enter circulation.
If the bone marrow-sinusoid system is a CLOSED system, how do newly made blood cells escape?
- A maturing BC or megakaryocye pushes against the endothelial cells of the sinusoid membrane.
- Fuses and pierces through the cell and forms an opening.
- Each blood cell must squeeze through to enter the lumen of the sinusoid.
- Afterwards, the cell will “Self-repair” and the opening closes to prevent immature cells from leaving,
Migration of BC across the bone marrow endothelium is what kind of event?
A transcellular event.
What are the 2 types of bone marrow?
- Red bone marrow
2. Yellow bone marrow
What is red bone marrow?
Where is it found?
What kind of cells if it made up of?
How do the cells organize?
Red bone marrow is an immature form found in the medullary cavity of long bones and spongy bone in young kids.
The hematopoietic cords are mainly developing BC and megakaryocyte (with some macrophages, mast and adipose cells)
Different types of blood cells will develop in clusters.
- erythrocytes and megakaryocytes develop in clusters near the wall of the sinusoid.
- granulocytes develop in clusters further from the wall.
The hematopoietic cords in red bone marrow are mainly what types of cells?
Developing blood cells and megakaryocytes.
Some macrophages, mast cells and adipose cells are present.
In red bone marrow, in what arrangement do blood cells develop?
They develop in clusters.
Erythrocytes and megakaryocytes develop in clusters near the wall of the sinusoids.
Granulocytes will develop in clusters further from the wall.
What is yellow bone marrow?
Yellow bone marrow is the type predominately in adults bone.
- Not as hematopoietically active.
- So, mainly adipose cells.
Yellow bone marrow has the ability to become hematopoietic again, by becoming red bone marrow.
How can yellow bone marrow become hematopoietic again (red bone marrow)?
HCS can repopulate.
As we age, we see a decrease/increase amount of adipose tissue compared to HCS.
Increase.
Active bone marrow contains what ratio of adipose and hemotopoetic tissue.
50:50
Active bone marrow is found in your
- ribs
- vertebrae
- pelvis
- shoulder.
What is the cellularity of bone marrow?
The ratio of HCS to adipocytes.
How can we find the cellularity of bone marrow?
Subtract a person age from 100 and add +/- 10%.
Ex. 30 years old.
100-30= 70% +/- 10%.= 60-80%
What is the cellularity of bone marrow important for?
It is important in looking at the fx of bone marrow BIOPSYs.
What is hypocellular marrow?
Small number of HCS.
High number of adipocytes.
What is hypocellular marrow indicative of?
Aplastic anemia or someone going through chemotherapy.
What is hypercellular marrow?
This bone marrow has been infected by hemopoetic cell tumors.
High number of HCS.
Low number of adipocytes.
What is hypercellular marrow indicative of?
Acute myelogenous leukemia.
What is a bone marrow aspirate?
A needle is inserted in the skin until it hits bone. Particularly, the posterior part of the iliac crest.
It is smeared and looked at. Unfortunately, this can fuck up the morphology of the cell.
What is a bone marrow core biopsy?
A needed it inserted in the bone and takes out a peice of INTACT bone marrow. This allows you to look at its architecture.
What controls proliferation and maturation of hematopoiesis?
Hematopoietic growth factors.
Where are hematopoietic growth factors made?
In bone marrow by
- Endothelial cells
- Stromal cells
- Fibroblasts
- Developing lymphocytes
- Macrophages.