Lecture 2: Hematopoiesis & Blood Forming Organs

Flashcards covering hematopoietic development, adult tissue structures, stem cell kinetics, cytokines, and the complete normoblastic maturation sequence and RBC morphology.

Hematopoiesis

The processes involved in stem cell self-renewal, proliferation, differentiation, and maturation of all blood cell lines to form functional blood cells.

Mesoblastic Phase

The first phase of hematopoietic development occurring in the yolk sac around the 19th day after fertilization.

Hepatic Phase

The second phase beginning at 5 to 7 gestational weeks, where the liver is the major hematopoietic organ during the second trimester.

Medullary Phase

The phase beginning between the 4th and 5th month of fetal development where the bone marrow (medulla) becomes the primary hematopoietic site.

Primitive Erythroblasts

Cells produced in the yolk sac during the mesoblastic phase; erythropoiesis is intravascular at this stage.

Gower I, Gower II, and Portland

The three types of embryonic hemoglobins present during the mesoblastic phase.

Definitive Hematopoiesis

The extravascular production of blood cells that begins during the hepatic phase.

HbF

Fetal hemoglobin; the main type of hemoglobin present during the hepatic phase.

HbA

Adult hemoglobin; starts appearing in small amounts during the hepatic phase and medullary phase.

Kupffer cells

Specialized macrophages located in the liver that play a role in hematopoiesis and other physiologic changes.

Thymus

A primary lymphoid organ responsible for T cell development in the fetal and adult stages.

Spleen and Kidney (Fetal)

Organs that contribute to B cell development during the hepatic phase.

Myeloid-to-erythroid (M:E) ratio

A measurement of bone marrow activity, reaching normal adult levels of $3:1 \text{ to } 4:1$ during the medullary phase.

Red Marrow

Hematopoietically active marrow; present in all bones during infancy and childhood.

Yellow Marrow

Hematopoietically inactive marrow composed mostly of fat cells or adipocytes.

Adipocytes

Fat cells that begin to increase in the marrow by age 4, replacing red marrow.

Marrow Cellularity

The ratio of red to yellow marrow in the bone cavity, which naturally decreases with age.

Bone Marrow Cellularity Formula

$$\% \text{ Cellularity} = 100 - \text{Age}$$

Bone Marrow Body Weight Range

The bone marrow accounts for $3.4\% \text{ to } 5.9\%$ of total body weight.

Bone Marrow Volume (KBW)

The bone marrow volume is estimated at $30-50\,mL/KBW$.

Active Sites (Late Adolescence)

Only flat bones, including the skull, vertebrae, pelvic, and sternum, remain hematopoietically active.

Posterior Iliac Crest

The primary site of the pelvis used for bone marrow specimen collection.

Bone Marrow Aspiration

A procedure used for cytologic typing, flow cytometry, and assessing hematopoietic cell proportions.

Bone Marrow Biopsy

A procedure used primarily to determine cellularity and detect certain disease states.

Iron Stain

A cytochemical stain used on BM samples for the detection of iron deficiency or iron overload.

Cytochemical Stains (Diagnosis)

Stains applied to BM samples specifically for the diagnosis of leukemias.

FISH

Fluorescent in situ hybridization; a staining method for the detection of gene mutations in marrow samples.

Flow Cytometry

A method used for the immunophenotyping of leukemias and lymphomas.

White Pulp

Splenic tissue containing follicles with lymphocytes, macrophages, dendritic cells, and germinal centers.

Red Pulp

Splenic tissue containing the cords of Billroth and specialized splenic macrophages.

Periarteriolar Lymphatic Sheath (PALS)

The region of the splenic white pulp where T cells are primarily located.

Germinal Centers

Areas within the splenic white pulp that contain activated B cells.

Culling

A splenic function involving the removal of old, damaged, or senescent erythrocytes.

Pitting

A splenic function involving the removal of inclusions from intact red blood cells.

Marginal Zone

The area surrounding the white pulp in the spleen containing memory B cells, macrophages, and CD4+ T cells.

Splenomegaly

The clinical term for an enlarged spleen.

Splenectomy

The surgical removal of the spleen; sometimes beneficial for conditions like HS, ITP, and AIHA.

Autosplenectomy

A pathophysiologic change where the spleen becomes non-functional over time due to disease (often sickle cell).

Hematopoietic Stem Cell (HSC)

An undifferentiated cell capable of self-renewal and pluripotency to reconstitute the hematopoietic system.

Pluripotent

The characteristic of a stem cell being able to differentiate into any blood cell lineage.

Common Myeloid Progenitor (CMP)

Differentiated progenitor cell also known as CFU-GEMM that gives rise to myeloid, erythroid, and megakaryocytic lines.

Common Lymphoid Progenitor (CLP)

Differentiated progenitor cell that gives rise to B, T, and Natural Killer cell lines.

Monophyletic Theory

The theory that all blood cell types originate from a single common hematopoietic stem cell.

Polyphyletic Theory

The theory suggesting that blood cell types originate from multiple separate stem cell sources.

Cytokines

Growth factors that regulate the survival, proliferation, and differentiation of hematopoietic cells.

Erythropoietin (EPO)

The primary cytokine responsible for the survival and maturation of erythroid progenitors.

TPO

Thrombopoietin; the cytokine involved in the development of megakaryocytes and platelets.

BFU-E

Burst-forming unit-erythroid; the earliest committed erythroid progenitor, which is less responsive to EPO.

CFU-E

Colony-forming unit-erythroid; a progenitor cell highly responsive to and dependent on EPO for survival.

Timeline: BFU-E to Mature RBC

A maturation process that takes approximately $18-21 \text{ days}$ in total.

Timeline: BFU-E to CFU-E

A maturation step that takes approximately one week.

Timeline: CFU-E to Pronormoblast

A maturation step that takes approximately one week.

Timeline: Pronormoblast to Mature RBC

The maturation sequence that takes around $6-7 \text{ days}$.

Basophilia

The blue color seen in stained cytoplasm due to high RNA content and protein synthesis activity.

Acidophilia

The salmon pink color in cytoplasm resulting from increasing hemoglobin concentration.

Sequential Change: Cell Diameter

The general reduction in the size of the cell as it matures from a pronormoblast to an erythrocyte.

Sequential Change: N/C Ratio

The decrease in the ratio of nuclear volume to cytoplasmic volume as the erythroid cell matures.

Pyknotic

A term describing a highly dense, shrunken, and non-functional nucleus seen in orthochromic normoblasts.

Normoblastic System

The terminology system using the names: Pronormoblast, Basophilic, Polychromatic, Orthochromic, Reticulocyte, and Erythrocyte.

Rubriblastic System

The terminology system using the names: Rubriblast, Prorubricyte, Rubricyte, Metarubricyte, and Erythrocyte.

Pronormoblast (Diameter)

Maturation stage with a diameter of $12-20\,\mu m$.

Pronormoblast (N/C Ratio)

Maturation stage with a Nuclear-to-Cytoplasmic ratio of $8:1$.

Pronormoblast (Nucleoli)

The stage containing $1-2$ nucleoli with an open chromatin pattern.

Golgi Zone

A pale area apparent in the deeply basophilic cytoplasm of the pronormoblast.

Basophilic Normoblast (Diameter)

Maturation stage with a diameter of $10-15\,\mu m$.

Basophilic Normoblast (N/C Ratio)

Maturation stage with a Nuclear-to-Cytoplasmic ratio of $6:1$.

Basophilic Normoblast (Cytoplasm)

Shows deep blue color, often even bluer than the previous stage, as hemoglobin is produced but obscured by RNA.

Polychromatic Normoblast (Diameter)

Maturation stage with a diameter of $10-12\,\mu m$.

Polychromatic Normoblast (Maturation Limit)

This stage is the last stage of erythroid cell division.

Polychromatic Normoblast (Cytoplasm)

Features a combination of blue (RNA) and pink (Hb), resulting in a blue-gray or polychromatic appearance.

Polychromatic Normoblast (N/C Ratio)

Stage where the Nuclear-to-Cytoplasmic ratio ranges from $4:1$ to $1:1$.

Orthochromic Normoblast (Diameter)

Maturation stage with a diameter of $8-10\,\mu m$.

Orthochromic Normoblast (N/C Ratio)

Stage with a low Nuclear-to-Cytoplasmic ratio of approximately $1:2$.

Orthochromic Normoblast (Cytoplasm)

The cytoplasm is close to salmon pink with a slight bluish hue from remaining RNA.

Orthochromic Normoblast (Lifespan)

This stage lasts for approximately $48 \text{ h}$ and is unable to divide.

Nuclear Ejection

The process occurring at the end of the orthochromic stage where the nucleus is expelled and engulfed by BM macrophages.

Reticulocyte (Morphology)

A cell with no nucleus, salmon pink cytoplasm with a bluish tinge, larger than an RBC, and not yet a biconcave disk.

Supravital Staining

A technique using dyes like New Methylene Blue or Brilliant Cresyl Blue to quantify reticulocytes.

Reticulocyte (Lifespan)

Resides for $1-2 \text{ days}$ in the bone marrow and $1 \text{ day}$ in the peripheral blood before maturing.

Polychromasia

The appearance of reticulocytes on a Wright-stained peripheral blood smear, looking bluish-gray.

Mature Erythrocyte (Diameter)

A biconcave disk normally measuring $7-8\,\mu m$ (based on diameter trends).

Mature Erythrocyte (Lifespan)

Functional blood cell that circulates for approximately $120 \text{ days}$.

Spherocytes

Abnormal RBCs that are sphere-shaped and lack the normal area of central pallor.

Acanthocyte

An RBC with an irregular distribution of spicules and frequently lacking central pallor.

Echinocyte

Also called a Burr cell; features an even distribution of crenations and usually shows central pallor.

Sickle Cells

Elongated, crescent-shaped RBCs caused by polymerized hemoglobin.

Schistocytes

Fragments of red blood cells caused by mechanical damage or microvascular environment changes.

Teardrop Cells

Dacrocytes; RBCs shaped like a drop of liquid.

Target Cells

Codocytes; cells with a dark center, light ring, and dark outer ring resembling a bullseye.

Ovalocytes

RBCs that are oval in shape rather than round.

Elliptocytes

RBCs characterized by an elongated, elliptical shape.

Stomatocytes

RBCs with a slit-like or mouth-like area of central pallor.

Howell-Jolly Bodies

Nuclear remnants (DNA) appearing as dark-staining inclusions in RBCs.

Basophilic Stippling

Tiny blue granules distributed throughout the RBC cytoplasm composed of RNA.

Cords of Billroth

Structure in the splenic red pulp where RBCs must pass through and undergo culling or pitting.

Hypocellular Bone Marrow

A state where the estimated cellularity is significantly lower than predicted for the patient's age.

Hypercellular Bone Marrow

A state where the estimated cellularity is significantly higher than predicted for the patient's age.

Stromal Cells

The cells in the medullary cavity that provide the microenvironment and support for developing hematopoietic cells.

Trabeculae

Bony structures radiating from the cortex of the bone that form a honeycomb structure for the marrow.

Primary Myeloid Site

The bone marrow becomes the primary site of hematopoiesis by the end of week 24 of gestation.