L4.1 HEMA - Blood Cell Morphology & Hematopoiesis

Hematopoiesis

↳ Is the process of blood cell production, differentiation, and development.

.

↳ Is the continuous, regulated process of renewal, proliferation, differentiation, and maturation of all blood cell lines.

.

↳ Hematopoietic stem cells (HSCs) are the foundation of the adult hematopoietic system.

differentiation

regulated

stem

adult

HEMATOPOIESIS:

.

↳ Is the process of blood cell production, ________________, and development.

.

↳ Is the continuous, ___________ process of renewal, proliferation, differentiation, and maturation of all blood cell lines.

.

↳ Hematopoietic ______ cells (HSCs) are the foundation of the _________ hematopoietic system.

Totipotential Stem Cells

Pluripotential Stem Cells

Multipotential Stem Cells

3 Types of Human Stem Cells

(TSC, PSC, MSC)

Totipotential Stem Cells

TYPES OF HUMAN STEM CELLS:

.

↳ Present in the first few hours after an ovum is fertilized.

hours

fertilized

TOTIPOTENTIAL STEM CELLS:

.

↳ Present in the first few ________ after an ovum is _____________.

Pluripotential Stem Cells

TYPES OF HUMAN STEM CELLS:

.

↳ Present several days after fertilization.

fertilization

PLURIPOTENTIAL STEM CELLS:

.

↳ Present several days after ___________________.

Multipotential Stem Cells

TYPES OF HUMAN STEM CELLS:

.

↳ Derived from pluripotent stem cells.

pluripotent

MULTIPOTENTIAL STEM CELLS:

.

↳ Derived from ________________ stem cells.

Erythropoiesis

Leukopoiesis

Granulopoiesis

Monopoiesis/Monocytopoiesis

Megakaryopoiesis

Lymphopoiesis

Thrombopoiesis

7 Terms under the Hematopoietic System

(E, L, G, M, M, L, T)

Erythropoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing RBCs; erythroid cells account for 5 - 38% of nucleated cells in normal marrow.

RBCs

38

normal

ERYTHROPOIESIS:

.

↳ Process of producing ______; erythroid cells account for 5 - ____% of nucleated cells in __________ marrow.

Leukopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing WBCs.

Granulopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing granulocytes; myeloid cells account for 23 - 85% of nucleated cells in normal marrow.

myeloid

85

GRANULOPOIESIS:

.

↳ Process of producing granulocytes; _____________ cells account for 23 - ____% of nucleated cells in normal marrow.

Monopoiesis/Monocytopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing monocytes.

Megakaryopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing megakaryocytes.

Lymphopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing lymphocytes; lymphoid cells account for 1 - 5% of nucleated cells in normal marrow.

5

LYMPHOPOIESIS:

.

↳ Process of producing lymphocytes; lymphoid cells account for 1 - __% of nucleated cells in normal marrow.

Thrombopoiesis

TERM UNDER THE HEMATOPOIETIC SYSTEM:

.

↳ Process of producing thrombocytes; develop into platelets approximately 5 days.

days

THROMBOPOIESIS:

.

↳ Process of producing thrombocytes; develop into platelets approximately 5 ________.

Mesoblastic Stage

Hepatic Stage

Medullary / Myeloid Phase

3 Phases of Hematopoiesis

Mesoblastic Stage

PHASES OF HEMATOPOIESIS:

.

↳ Happens 2 to 8 weeks of life in the yolk sac.

.

↳ Produces primitive RBCs (Erythroblasts).

.

↳ Production of embryonic hemoglobin.

weeks

yolk

primitive

embryonic

MESOBLASTIC STAGE:

.

↳ Happens 2 to 8 _________ of life in the _______ sac.

.

↳ Produces ____________ RBCs (Erythroblasts).

.

↳ Production of ______________ hemoglobin.

Hepatic Stage

PHASES OF HEMATOPOIESIS:

.

↳ 5 to 7 weeks of life and happens in the liver.

.

…..➙ 3rd Month = Granulopoiesis and Megakaryopoiesis

.

…..➙ 4th Month = Lymphopoiesis

.

…..➙ 5th Month = Monocytopoiesis

7

liver

Megakaryopoiesis

Lymphopoiesis

Monocytopoiesis

HEPATIC STAGE:

.

↳ 5 to ___ weeks of life and happens in the _________.

.

…..➙ 3rd Month = Granulopoiesis and ____________________

.

…..➙ 4th Month = _______________

.

…..➙ 5th Month = ______________________

Medullary / Myeloid Phase

PHASES OF HEMATOPOIESIS:

.

↳ 5th month of gestation and happens in the bone marrow.

.

↳ Bone cavities begin to form.

5th

marrow

cavities

MEDULLARY / MYELOID PHASE:

.

↳ ____ month of gestation and happens in the bone ____________.

.

↳ Bone ___________ begin to form.

Hematopoietic Tissues

↳ Can be medullary hematopoiesis or extramedullary hematopoiesis.

extramedullary

HEMATOPOIETIC TISSUES:

.

↳ Can be medullary hematopoiesis or ________________ hematopoiesis.

Bone Marrow

Liver

Spleen

Lymph Nodes

Thymus

5 Hematopoietic Tissues

(BM, L, S, LN, T)

Bone Marrow

UNDER HEMATOPOIETIC TISSUES:

.

↳ One of the largest organs in the body.

.

↳ Composed of two major components:

.

…..➙ Red Marrow and Yellow Marrow

.

↳ The process of replacing the active marrow by adipocytes (yellow marrow) during development is called retrogression.

largest

Yellow

adipocytes

retrogression

BONE MARROW:

.

↳ One of the ______________ organs in the body.

.

↳ Composed of two major components:

.

…..➙ Red Marrow and ___________ Marrow

.

↳ The process of replacing the active marrow by _________________ (yellow marrow) during development is called ___________________.

Liver

UNDER HEMATOPOIETIC TISSUES:

.

↳ Serves as the major site of blood cell production during the second trimester of fetal development.

.

↳ Kupffer Cells are macrophages that remove senescent cells and foreign debris from the blood that circulates through the liver; they are also secret mediators that regulate protein synthesis in the hepatocytes.

production

second

Kupffer

senescent

liver

protein

LIVER:

.

↳ Serves as the major site of blood cell _______________ during the __________ trimester of fetal development.

.

↳ ___________ Cells are macrophages that remove _____________ cells and foreign debris from the blood that circulates through the _______; they are also secret mediators that regulate _________ synthesis in the hepatocytes.

Spleen

UNDER HEMATOPOIETIC TISSUES:

.

↳ The largest lymphoid organ in the body, lies beneath the diaphragm behind the fundus of the stomach in the upper left quadrant of the abdomen.

.

↳ In a healthy individual, the spleen contains about 350 mL of blood.

.

↳ Hypersplenism is an enlargement of it resulting in some degree of pancytopenia despite the presence of a hyperactive bone marrow.

lymphoid

fundus

left

350

Hypersplenism

pancytopenia

hyperactive

SPLEEN:

.

↳ The largest _____________ organ in the body, lies beneath the diaphragm behind the _________ of the stomach in the upper ______ quadrant of the abdomen.

.

↳ In a healthy individual, the spleen contains about _________ mL of blood.

.

↳ _______________ is an enlargement of the spleen resulting in some degree of ________________ despite the presence of a ______________ bone marrow.

Lymph Nodes

UNDER HEMATOPOIETIC TISSUES:

.

↳ Bean-shaped structures (1 to 5 mm in diameter) are typically present in groups or chains at various intervals along lymphatic vessels.

.

↳ Adenitis = Infection or inflammation of the it.

.

↳ More serious is the common entry into the lymph nodes of malignant cells that have broken loose from malignant tumors.

Bean

5

chains

lymphatic

Adenitis

entry

broken

LYMPH NODES:

.

↳ ________-shaped structures (1 to ___ mm in diameter) are typically present in groups or ________ at various intervals along _____________ vessels.

.

↳ ___________ = Infection or inflammation of the it.

.

↳ More serious is the common _________ into the lymph nodes of malignant cells that have ___________ loose from malignant tumors.

Thymus

UNDER HEMATOPOIETIC TISSUES:

.

↳ At birth, the it is an efficient, well-developed organ.

.

↳ In adults, T cell progenitors migrate to it from the bone marrow for further maturation.

.

↳ It consists of two lobes, each measuring 0.5 to 2 cm in diameter, and is further divided into lobules.

.

↳ Nondevelopment of it during gestation results in the lack of formation of T lymphocytes.

efficient

T

maturation

two

2 cm

lobules

gestation

lymphocytes

THYMUS:

.

↳ At birth, the it is an ___________, well-developed organ.

.

↳ In adults, ___ cell progenitors migrate to it from the bone marrow for further ________________.

.

↳ It consists of ______ lobes, each measuring 0.5 to ______ in diameter, and is further divided into ___________.

.

↳ Nondevelopment of it during ______________ results in the lack of formation of T _________________.

Stem Cell Theory

↳ Till and McCulloch (1961)

.

…..➙ Conducted experiments on mice creating a state of aplasia.

.

…..➙ Aplastic mice were given an intravenous injection of marrow cells.

.

…..➙ Colonies of HSCs were seen 7 to 8 days later in the spleens of the irradiated mice and called CFU-S.

.

…..➙ CFU-S represents committed myeloid progenitors or CFU-GEMM.

.

↳ Originally, there were two theories describing the origin of hematopoietic progenitor cells.

.

…..➙ Monophyletic Theory and Polyphyletic Theory

.

↳ HSCs are directed to one of three possible fates: self-renewal, differentiation, or apoptosis.

.

↳ When the HSC divides, it gives rise to two identical daughter cells.

McCulloch

61

aplasia

intravenous

days

spleens

CFU-S

myeloid

GEMM

progenitor

STEM CELL THEORY:

.

↳ Till and _______________ (19___)

.

…..➙ Conducted experiments on mice creating a state of ___________.

.

…..➙ Aplastic mice were given an _________________ injection of marrow cells.

.

…..➙ Colonies of HSCs were seen 7 to 8 ________ later in the ________ of the irradiated mice and called _______.

.

…..➙ CFU-S represents committed ___________ progenitors or CFU-________.

Polyphyletic

renewal

apoptosis

identical

STEM CELL THEORY:

.

↳ Originally, there were two theories describing the origin of hematopoietic ______________ cells.

.

…..➙ Monophyletic Theory and ________________ Theory

.

↳ HSCs are directed to one of three possible fates: self-___________, differentiation, or _____________.

.

↳ When the HSC divides, it gives rise to two _____________ daughter cells.

Cytokines and Growth Factors

↳ A group of specific glycoproteins called hematopoietic growth factors or cytokines regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells.

.

↳ Are a diverse group of soluble proteins that have direct and indirect effects on hematopoietic cells.

.

↳ Are responsible for stimulation or inhibition of production, differentiation, and trafficking of mature blood cells and their precursors.

.

↳ Prevent hematopoietic precursor cells from dying by inhibiting apoptosis.

glycoproteins

precursor

soluble

effects

stimulation

trafficking

apoptosis

CYTOKINES AND GROWTH FACTORS:

.

↳ A group of specific _________________ that regulate the proliferation, differentiation, and maturation of hematopoietic ______________ cells.

.

↳ Are a diverse group of __________ proteins that have direct and indirect ___________ on hematopoietic cells.

.

↳ Are responsible for _______________ or inhibition of production, differentiation, and _______________ of mature blood cells and their precursors.

.

↳ Prevent hematopoietic precursor cells from dying by inhibiting _____________.

EPO

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Kidney (peritubular interstitial cell).

G-CSF

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Endothelial cells, placenta, monocytes and macrophages.

GM-CSF

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ T-cells, macrophages, endothelial cells, fibroblasts and mast cells.

IL-2

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ CD4 T cells, NK cells and B cells.

IL-3

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Activated T cells and NK cells.

IL-6

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ T cells, macrophages and fibroblasts.

IL-10

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ CD4, Th2 T cells, CD8 T cells, monocytes and macrophages.

IL-12

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Macrophages.

IL-15

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Activated CD4 and T cells.

IFN α

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Dendritic cells, NK cells, T cells, B cells, macrophages, fibroblasts, endothelial cell and osteoblasts.

CD2, CD3

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Lymphoid, Pan T cells

CD4

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Helper/Inducer T Cells

CD5/CD7

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ T-lymphoid

CD8

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Suppressor/Cytotoxic T Cell

CD13, CD33

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Pan Myeloid

CD10

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ B-lymphoid

CD11c, CD14

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Monocytes

CD19, CD20

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Lymphoid, Pan B Cells

CD16, CD56

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ NK Cells

CD34

COMMONLY USED MARKERS (CYTOKINES AND GROWTH FACTORS):

.

↳ Stem Cell Marker (Lymphoid and Myeloid Precursor)

Bone Marrow

Thymus

Antigen-Independent Lymphopoiesis

3 Primary Lymphoid Tissue

(BM, T, AIL)

Bone Marrow.

PRIMARY LYMPHOID TISSUE:

.

↳ Site of pre-B cell differentiation.

Thymus.

PRIMARY LYMPHOID TISSUE:

.

↳ Site of pre-T cell differentiation.

Secondary Lymphoid Tissue

↳ B and T lymphocytes enter the blood and populate secondary lymphoid tissue, where antigen contact occurs.

.

↳ Includes lymph nodes, spleen, GALT / Peyer's Patches.

.

↳ Antigen-Dependent Lymphopoiesis

blood

antigen

spleen

Patches

Dependent

SECONDARY LYMPHOID TISSUE:

.

↳ B and T lymphocytes enter the _________ and populate secondary lymphoid tissue, where __________ contact occurs.

.

↳ Includes lymph nodes, ________, GALT / Peyer's __________.

.

↳ Antigen-_______________ Lymphopoiesis