Week 3 Lec: Hematopoiesis Flashcards
When does hematopoiesis stop?
only after death
It is a continuous, regulated process of blood cell production.
Hematopoiesis
Hematopoiesis is a continuous, regulated process of blood cell production that includes?
- cell renewal
- proliferation
- differentiation
- maturation
What are the two developments of hematopoiesis?
- Pre-natal
- Post-natal
Pre-natal development is also called as?
Embryonic/Fetal Development
Post-natal development is also called as?
Adult Development
3 phases of pre-natal development?
Mesoblastic, Hepatic, and Medullary phase
Other name for mesoblastic phase?
Primitive hematopoiesis/Yolk sac phase
When does the mesoblastic phase begin?
begins around the 19th day of embryonic development after fertilization
Primitive erythrocytes from the mesoblastic phase arise from?
mesodermal cells
The cells from the mesoderm migrate to the _________ and become primitive erythrocytes.
yolk sac
Transient yolk sac erythroblasts are important in early ________ to produce ________ .
embryogenesis; hemoglobin
What are the 3 embryonic hemoglobins that are important in transporting oxygen?
Gower-1, Gower-2, and Portland
What globin chain starts its production at the mesoblastic phase?
Alpha globin chain
Globin chain combination of Gower I?
2 epsilon, 2 zeta
Globin chain combination of Gower II?
2 alpha, 2 epsilon
Globin chain combination of Portland?
2 zeta, 2 gamma
If the globin chain combination has only 1 instead of 2 epsilons, for example, what condition could occur?
Thalassemia
Other name for hepatic phase?
Definitive hematopoiesis
When does hepatic phase begin?
begins at 5 to 7 gestational weeks
The hepatic phase is characterized by?
recognizable clusters of developing erythroblasts, granulocytes, and monocytes colonizing the fetal liver, thymus, spleen, placenta
The developing erythroblasts signal the beginning of __________ with a decline in __________ of the yolk sac.
definitive hematopoiesis; primitive hematopoiesis
Hematopoiesis during hepatic phase occurs __________, with the _____ remaining the major site of hematopoiesis during the second trimester of fetal life.
extravascularly; liver
What type of hemoglobin is present during the hepatic phase?
Hemoglobin F and A
The developing _____,_____,_____, and _____ contribute to the hematopoietic process during hepatic phase.
spleen, kidney, thymus, and lymph nodes
_____, the first fully developed organ in the fetus, is the major site of _____.
Thymus; T cell production
_____ produce B cells during hepatic phase.
Kidney and Spleen
Kidney and Spleen produce _____ during hepatic phase.
B cells
Globin chain combination of Hemoglobin F?
2 alpha, 2 gamma
During the _____ month of fetal development, hematopoiesis begins in the bone marrow cavity.
fifth
During the fifth month of fetal development, hematopoiesis begins in the ________.
bone marrow cavity
Other name for medullary phase?
Myeloid phase
Hematopoietic activity, especially myeloid activity, is apparent during this stage of development, and the myeloid-to-erythroid ratio gradually approaches __________.
3:1 (adult levels)
Measurable levels of _____, _____, _____, _____, and _____ can be detected during medullary phase.
erythropoietin (EPO)
(G-CSF)
(GM-CSF)
hemoglobins F and A
A growth factor stimulating the production of RBC.
Erythropoietin
Where is the source of erythropoietin?
Kidney
They stimulate the production of granulocytes.
G-CSF and GM-CSF
Chief site of the medullary phase?
bone marrow
Globin chain combination of Hemoglobin A?
2 alpha, 2 beta
Globin chain combination of Hemoglobin A2?
2 alpha, 2 delta
What is the degradation product of hemoglobin A?
Hemoglobin A2
In adults, hematopoietic tissue is located in the?
– bone marrow
– lymph nodes
– spleen, liver
– thymus
The bone marrow of adults contain developing?
erythroid, myeloid, megakaryocytic, and lymphoid cells
What do you call the hematopoietic cells responsible for RBCs?
erythroid
What do you call the hematopoietic cells responsible for granulocytes?
myeloid
What do you call the hematopoietic cells responsible for the production of platelets?
megakaryocytic
Lymphoid development occurs in ______ and _____ lymphoid tissue.
primary; secondary
Primary lymphoid tissue is located in?
bone marrow and thymus
This is where T and B lymphocytes are derived.
Thymus
This is where lymphoid cells respond to foreign antigens.
Secondary lymphoid tissue
Secondary lymphoid tissue consists of?
- spleen
- lymph nodes
- mucosa-associated lymphoid tissue
Give the primary locations of bone marrow in adult humans.
Ribs
Sternum, Skull, Scapula
Vertebra
Pelvis
Organs involved in post-natal development?
- Bone marrow
- Liver
- Spleen
- Lymph Nodes
- Thymus
It is one of the largest organs in the body.
Bone Marrow
Major function of bone marrow?
proliferation and production of blood cells
Two major components of Bone Marrow?
Red marrow and Yellow marrow
It is the hematopoietically active marrow consisting of the developing blood cells and their progenitors (flat bones of the skull, clavicle, sternum, ribs, vertebrae and pelvis).
Red marrow
These are “undifferentiated cells”.
progenitors
2 types of progenitors?
common myeloid progenitor and common lymphoid progenitor
4 Main Functions of Red Bone Marrow?
– Production of blood cells
– Destruction of erythrocytes
– Iron storage (from Hb breakdown)
– Central organ for B lymphocyte development
It is the hematopoietically inactive marrow composed primarily of adipocytes and (fat cells), with undifferentiated mesenchymal cells and macrophages.
Yellow marrow
________ becomes abundant during 5 and 7 years of age where they occupy the spaces in the long bones previously dominated by red marrow.
Yellow marrow
Yellow marrow becomes abundant during ____________ where they occupy the spaces in the long bones previously dominated by red marrow.
5 and 7 years of age
The process of replacing the active marrow by adipocytes (yellow marrow) during development is called ___________.
retrogression
Yellow marrow is capable of reverting back to active marrow in cases of increased demand on the bone marrow, such as in _____________.
excessive blood loss or hemolysis
Plays an important role in stem cell differentiation and proliferation.
Hematopoietic Microenvironment
It is responsible for supplying semifluid matrix (stroma) that serves as an anchor for the developing hematopoietic cells.
Hematopoietic Microenvironment
It is a semifluid matrix that serves as an anchor for the developing hematopoietic cells.
Stroma
Composition of Stroma?
- Endothelial cells
- Adipocytes
- Macrophages
- Osteoblasts
- Osteoclasts
- Reticular cells (fibroblasts)
They regulate the flow of particles entering and leaving hematopoietic spaces.
Endothelial cells
They secrete various steroids that influence erythropoiesis and maintain bone integrity and regulates the volume of marrow.
Adipocytes
They function in phagocytosis and secretion of various cytokines that regulate hematopoiesis.
Macrophages
They are bone-forming cells that have water bug or comet appearance (plasma cell).
Osteoblasts
Osteoblasts have a _______ appearance.
water bug or comet
They are bone resorbing cells or destroying cells.
Osteoclasts
They support the vascular sinuses and hematopoietic cells.
Reticular Cells (fibroblasts)
Composition of Extracellular Matrix of BM?
- Proteoglycans/Glycosaminoglycans
- Fibronectin
- Collagen
- Laminin
- Hemonectin
- Thrombospondin
The composition of the extracellular matrix of the bone marrow are for?
adhesion to the hematopoietic environment; if no adhesion takes place, then structural integrity will be destroyed
_____ serves as the major site of blood cell production during the second trimester of fetal development.
Liver
The liver is capable of ___________ hematopoiesis.
extra medullary
Functions of the liver?
– protein synthesis and degradation, coagulation factor synthesis, carbohydrate and lipid metabolism
– drug and toxin clearance
– iron recycling and storage
– hemoglobin degradation
– enzyme activation
– storage of glycogen, vitamins, and minerals
It is the largest lymphoid organ in the body.
Spleen
Where is the spleen located?
It is located directly beneath the diaphragm behind the fundus of the stomach in the upper left quadrant of the abdomen.
True or False: The spleen is vital but not essential for life.
True
Functions of the spleen?
– indiscriminate filter of the circulating blood
– serves as a storage site for platelets
If there is no spleen, then there is no storage site for platelets, which could result to __________.
thrombocytosis
3 Regions of Spleen?
- White pulp
- Red pulp
- Marginal zone
It is the region of the spleen that consists of scattered follicles with germinal centers containing lymphocytes, macrophages, and dendritic cells.
White pulp
The region of the spleen that is involved in the normal immune system and responds to infection.
White pulp
It is the region of the spleen composed primarily of vascular sinusoids and sinuses separated.
Red pulp
The region of the spleen responsible for the removal of old, damaged, and dead RBCs.
Red pulp
This region of the spleen surrounds the white pulp and forms a reticular meshwork containing blood vessels, macrophages, and specialized B cells.
Marginal zone
Two methods for removing senescent or abnormal RBCs from the circulation?
- Culling
- Pitting
Method of removing RBCs in which cells are phagocytized with subsequent degradation of cell organelles.
Culling
Method of removing RBCs in which splenic macrophages remove inclusions or damaged surface membrane from the circulating RBCs.
Pitting
They are members of lymphatic system located along the lymphatic capillaries.
Lymph Nodes
Shape and size of lymph nodes?
bean-shaped structures (1-5 mm)
Functions of lymph nodes?
- Play a role in the formation of new lymphocytes from germinal centers.
- Involved in the processing of specific Ig.
- Involved in the filtration of particulate matter, debris, and bacteria entering the lymph node via the lymph.
3 regions of the lymph nodes?
- Cortex
- Medulla
- Paracortex
The outer region of the lymph node that contains follicles of B cells.
Cortex
The cortical region of some follicles develop foci of activated B cell proliferation called ______.
germinal centers
The inner region of the lymph node that consists primarily of T lymphocytes and plasma cells.
Medulla
The region between cortex and medulla that contains predominantly T cells and numerous macrophage.
Paracortex
This organ originates from endodermal and mesenchymal tissues.
Thymus
Thymus originates from _____ and _____.
endodermal and mesenchymal tissues
It is an efficient, well-developed organ at birth that consist of two lobules each measuring 0.5 to 2 cm in diameter.
Thymus
Is the organ responsible in the conditioning of T lymphocytes.
Thymus
They are cells that have extensive proliferative capacity.
Stem cell
Stem cells have the ability to?
- Ability to give rise to new stem cell
- Ability to differentiate into any blood cells lines
___ and ___ are capable of producing all types of blood cells.
HSC; BMC
Stem cells differentiate into one or another type of committed stem cells called ________.
progenitor cells
3 Possible Activities of HSCs?
- Self-renewal
- Differentiation
- Apoptosis
It refers to programmed cell death. A normal physiologic process that eliminates unwanted, abnormal, or harmful cells.
Apoptosis
Two theories describing the origin of hematopoietic progenitor cells?
- Monophyletic Theory
- Polyphyletic Theory
This theory is what we currently use and suggests that all blood cells derived from a single progenitor stem cell called pluripotent HSC.
Monophyletic Theory
Monophyletic theory is what we currently use and suggests that all blood cells derived from a single progenitor stem cell called ________.
pluripotent HSC
This theory suggests that each of the blood cell lineage is derived from its own unique stem cell.
Polyphyletic Theory
Enumerate the Hematopoietic Growth Factors.
- CSF: Colony Stimulating Factors
a. GM-CSF
b. G-CSF
c. M-CSF
d. Meg-CSF - Erythropoietin (EPO)
- Thrombopoietin
These hematopoietic growth factors are specific for various cell lines.
CSF/Colony Stimulating Factors
A pan myeloid growth factor that stimulates Granu, -mono, megakaryocyte, and eosinophil progenitors.
GM-CSF/Granulocyte macrophage colony-stimulating factor
Sources of GM-CSF?
fibroblast, T cells, and endothelial cells
These hematopoietic growth factors stimulate granulocytes production and functional activation.
G-CSF/Granulocyte colony-stimulating factor
Sources of G-CSF?
monocytes and fibroblast
These hematopoietic growth factors stimulate monocytes and macrophages production activity.
M-CSF/Macrophage colony-stimulating factor
Sources of M-CSF?
monocytes, fibroblast, and endothelial cells
Sources of Meg-CSF/Megakaryocyte colony-stimulating factor?
mono, fibroblast, and megakaryocytes
This hematopoietic growth factor that stimulates proliferation, growth and differentiation of erythroid precursors and may have minor effects on megakaryocytes.
Erythropoietin (EPO)
Target cells of erythropoietin?
pronormoblast and CFU-Erythroid (Colony forming unit-erythroid) cells
Source of EPO?
kidney
Hypoxia causes increased?
EPO production
Increased EPO production is caused by?
hypoxia
This hematopoietic growth factor regulates production of platelets.
Thrombopoietin
Source of thrombopoietin?
Mainly liver, but few is in the kidney
The entry of mature blood cells into the intravascular space relies upon?
- Multiplication of developing cells
- Gradual maturation
- Orderly release of cell from bone marrow
It is a group of specific glycoproteins called growth factors that regulates the proliferation, differentiation, and maturation of hematopoietic precursor cells.
Cytokines
Cytokines include?
- Interluekins (Ils)
- Lymphokines
- Monokines
- Interferons
- Colony Stimulating Factors (CSFs)
- Chemokines
Positive Influence Cytokines include?
- IL-1
- IL-3
- IL-6
- IL-9
- IL-11
- GM-CSF
- Kit Ligand
Interleukin for inflammation?
IL-1
Interleukin for regulation of growth and diferentiation of hematopoietic progenitors?
IL-3
Interleukin for infection and platelet production?
IL-6
Interleukin that promotes mast cell growth and its function.
IL-9
Interleukin that stimulates erythropoiesis.
IL-11
Interleukins for the differentiation of platelets.
IL-3,6,11
Positive influence cytokine for binding?
Kit Ligand
Negative Influence Cytokines include?
- Transforming Growth Factor-β
- Tumor Necrosis Factor-α
- Interferons
The spleen is also called the _________ because all dead cells travel and stay here.
graveyard
In a healthy individual, approximately ____ of the total platelet count is sequestered in the spleen.
30%
The spleen has a rich blood supply receiving approximately ___/min.
350 mL
During fetal development, the restricted, sequential distribution of cells is initiated in the yolk sac and then progresses in the _______________ region.
aorta-gonad-mesonephros (AGM) region (mesoblastic phase)
Some body organs, such as the thymus, undergo _______ when the human becomes an adult.
atrophy
Life span of red blood cells/erythrocytes?
120 days