Hema 1: hematopoiesis

Hemopoiesis

Hematopoiesis aka: ___

Hematopoiesis

Process of blood formation

CD34

Classical marker of hematopoietic stem cells

Nineteenth day

Hematopoiesis is considered to start around the ____ of embryonic development after fertilization

Light Amplified by Stimulated Emission of Radiation

⭐ Decode LASER

Polyphyletic theory

This theory suggests that each of the blood cell lineages is derived from its own unique stem cell.

Monophyletic theory

It suggests that all blood cells are derived from a single progenitor stem cell called a pluripotential stem cell

Pluripotential Stem Cell (PSC)

Single progenitor stem cell where all blood cells are derived from

Monophyletic theory

Most widely accepted theory for the origin of hematopoietic progenitor cells among experimental hematologists

Yolk sac

Chief site of hematopoiesis in Mesoblastic/Megaloblastic phase

Fetal liver (with some contributions by spleen, thymus, and lymph nodes)

Chief site of hematopoiesis in Hepatic phase

Bone marrow

Chief site of hematopoiesis in the Intramedullary/Medullary/Myeloid phase

Mesoblastic/Megaloblastic phase

Hematopoietic phase in the first 2 to 8 weeks of life

Primitive erythroblasts

First ever RBCs formed in life

2.) Gower-1, Gower-2, and Portland

Important in early embryogenesis to produce hemoglobin (_) necessary for delivery of oxygen to the embryonic tissues

Yolk sac hematopoiesis occurs intravascularly (within developing blood vessels)

How does yolk sac hematopoiesis differ from hematopoiesis that occurs later (fetal and adult stage)?

Hb F (Fetal hemoglobin)

The predominant hemoglobin in Hepatic phase of Hematopoiesis

Hepatic phase

Hb F is formed in what phase of hematopoiesis

Thymus

⭐The first fully developed organ in the fetus

Increases

The size of the thymus ___ during fetal development

Thymus

Major site of T cell production

Kidneys and Spleen

Organs that produce B cells

Before the 5th month of fetal development

Hematopoiesis starts in the bone marrow cavity ____.

bone marrow

The chief site of hematopoiesis by the end of 24 weeks gestation

Bone marrow

It contains developing erythroid, myeloid, lymphoid, and megakaryocytic cells.

bone marrow

Considered to be a primary lymphoid organ

Bursa of Fabricius (birds)

The bone marrow is said to have functions equivalent to that of ___.

It is not a normal hematopoietic organ in a normal situation, only in abnormal conditions does it produce blood cells (lymphocytes).

Describe liver as a hematopoietic organ

Retrogression

The process of replacing red marrow by yellow marrow during development

Between 5 and 7 years of age

When does retrogression occur?

Yes, in cases of increased demand on the bone marrow (example: excessive blood loss and hemolysis) and in such instance, the percentage of red to yellow marrow is not equal anymore.

Does the yellow marrow have the ability of reverting back to active/red marrow?

Red marrow

The hematopoietically active marrow

Yellow marrow

The hematopoietically inactive marrow composed primarily of fat cells (adipocytes)

Bone marrow and Thymus

The primary lymphoid organs

BM

Lymphoid cells fated to become B cells undergo their early stages of differentiation within the ___.

Spleen and Lymph nodes

The major secondary lymphoid organs

Gastrectomy

Surgical removal of the stomach which leads to anemia

Spleen

Largest of the secondary lymphoid organs

Spleen

Major organ in the body in which antibodies are synthesized and from which they are released into the circulation

Often leads to an increased incidence of bacterial sepsis caused primarily by S. pneumoniae, N. meningitidis, and H. influenzae

Effects of splenectomy in Children

Less adverse effects, although it leads to some increase in blood-borne bacterial infections or bacteremia

Effects of splenectomy in Adults

More severe

The effect of splenectomy is ___ in children than in adults.

Splenectomy

Refers to the removal of the spleen

Splenomegaly

Refers to the enlargement of the spleen

Lymph nodes

Small ovoid, bean-shaped structures (normally <1 cm in diameter) found in different areas throughout the body

Lymphoma

Solid tumor neoplasm of lymphoid tissue

Tonsils

Detect and respond to antigens in the respiratory and alimentary secretions

Peyer's patches

Clusters of lymphocytes distributed in the lining of the small intestine

Peyer's patches

Detect substances that diffuse across the intestinal epithelium

MALT (Mucosa-associated lymphoid tissue)

General term for the unencapsulated lymphoid tissues present in regions underlying the mucosal areas

2.) Extramedullary hematopoiesis

⭐ Can maintain hematopoietic stem cells and progenitor cells to generate various blood cells (a process called ____) as a response to infectious agents or in pathologic myelofibrosis of the bone marrow

Posterior superior and anterior superior iliac crest

Preferred sites for BM aspiration in adults

Anterior medial surface of the tibia

Preferred site for BM aspiration in children (< 2 years old)

At least 500 cells (preferably 1,000 cells) be counted on each of 2 slides

Recommended number of cells to be counted for Marrow Differential

Bone marrow aspirate

Disturbs bone marrow architecture and spread as a smear on a slide, stained, and examined for hematologic or systemic disease

BM aspirate

BM species used for analysis of individual cell morphology

10 years

Bone marrow smears should be retained for ___.

M:E (myeloid-to-erythroid) ratio

Proportion of myeloid cells to nucleated erythroid precursors in the bone marrow aspirate

monocytic and lymphoid precursors and plasma cells

These are excluded from the myeloid cell count

1.5:1 to 3.3:1

In healthy individuals, the M:E ratio varies from roughly ____.

10:1

⭐ M:E ratio in leukemia (Harr)

Bone marrow biopsy

Bone marrow removed intact without disturbing the bone architecture

Gives a better picture of the real structure of bone marrow

Advantage of a bone marrow biopsy

BM biopsy

Used for analysis of bone marrow architecture

Bone marrow aspirate - BM architecture is disturbed, whereas, Bone marrow biopsy - BM architecture isn't disturbed

Compare Bone marrow aspirate and Bone marrow biopsy

Extramedullary hematopoiesis

Refers to blood cell production outside the bone marrow

a. Extramedullary hematopoiesis in the liver and spleen

⭐ When a patient has severe anemia and the bone marrow is unable to effectively produce red blood cells to meet the increased demand, one of the body's responses is:

Erythropoiesis

Process of RBC formation (takes place inside the bone marrow)

Erythron

Total mass of RBCs circulating in the peripheral blood and the bone marrow RBC precursors

RBC mass

Erythrocytes in the circulation

Erythrokinetics

A term that describes the dynamics of RBC creation and destruction

Spleen

⭐ "Graveyard" of RBCs

Ineffective erythropoiesis

Refers to the production of defective erythroid precursor cells

Apoptosis

Defective RBC precursors often undergo __ in the bone marrow before they have a chance to mature to the reticulocyte stage

Apoptosis

Programmed cell death

Insufficient erythropoiesis

Refers to the decrease in the number of RBC precursors in the bone marrow (resulting in decreased RBC production)

Progenitor cells

Immature hematopoietic cell that is committed to a cell line but cannot be identified morphologically (Ex. BFU-E, CFU-E)

Precursor cells

Immature hematopoietic cell that is morphologically identifiable as belonging to a given cell line (Ex. Rubriblast, Prorubricyte)

CD71

Earliest marker of erythroid differentiation

Transferrin receptor

CD71 is the earliest marker of erythroid differentiation and a ___

Transferrin

Protein that transports iron in the blood

EPO (Erythropoietin)

Chief stimulatory cytokine for RBCs

EPO (Erythropoietin)

Major hormone that stimulates the production of erythrocytes

Thermostable, nondialyzable, glycoprotein hormone

EPO is a _ hormone.

Kidney

Organ that produces EPO

Peritubular interstitial cell (kidneys)

Primary cell source of EPO

BFU-E and CFU-E

Primary target cells of EPO

Apoptosis

The major way in which EPO increases RBC mass

Blood doping

Some athletes illegally use EPO injections to increase the oxygen-carrying capacity of their blood (to enhance endurance and stamina) which can lead to deadly arterial and venous thrombosis, this illegal practice is referred to as ___.

Pituitary gland

Growth hormone is produced by ___.

Directly

GH stimulates erythropoiesis ____.

Directly (stimulates BM)

Testosterone is produced by ___.

Indirectly (It goes to kidney and stimulates it [rather than bm] to produce more EPO to stimulate BM)

Testosterone stimulates erythropoiesis ___.

Pituitary gland

Prolactin is produced by ___.

Directly

Prolactin stimulates erythropoiesis ___.

Ovaries

Estrogen is produced by ___.

Inhibits erythropoiesis indirectly

How does estrogen affect erythropoiesis?

Hormones (testo and estro)

The reason behind difference in RBC count between males (higher) and females

BFU-E (Burst forming unit-erythroid)

The earliest committed erythroid progenitor cell

BFU-E and CFU-E (Colony forming unit-erythroid)

The committed erythroid progenitor cells