introduction to hematopoiesis

hematopoiesis

process by which pluripotent hematopoietic stem cells differentiate into myeloid or lymphoid precursor cells and eventually mature into blood cells

hematopoietic stem & progenitor cells (HSPC)

cells expressing transmembrane protein CD34- marker to identify & enrich hematopoietic stem cells in bone marrow transplantation

have 2 essential properties for maintenance of hematopoiesis:

• pluripotency

• self-renewal capacity

myeloid precursor cells

cells that develop into erythrocytes, granulocytes, or megakaryocytes

lymphoid precursor cells

cells that develop into lymphocytes or natural killer cells

dendritic cells

cells that may derive from myeloid or lymphoid precursors

red blood cells

cells that carry O₂ & CO₂

• histology: central pallor about 1/3 the diameter of cell

• senescent cells are phagocytosed in spleen by macrophages → produces unconjugated bilirubin

platelets

cells involved in hemostasis (1/3 held in spleen)

fragment of megakaryocytes

leukocytes

neutrophils, lymphocytes, monocytes, eosinophils, & basophils

neutrophils

acute response & bacteria

macrophages

ingest bacteria, cell debris, & old RBCs

basophils & mast cells

immediate reaction of innate immune system (IgE)

eosinophils

parasite infections & allergic reactions

B cells

humoral immunity (antibodies & memory cells after exposure)

T cells

cellular immunity; form in morrow, mature in thymus

• killer/cytotoxic

• helper

normal bone marrow

cellularity approximately 50% normal ration of myeloid to erythroid = ~3:1

contains:

• granulocyte precursors (myeloblasts, promyelocytes, myelocytes, & metamyelocytes)

• erythroid percurors

• megakaryocytes

erythropoiesis

process of red blood cell production in different stages during development

sites of production embryogenesis/fetal development

• week 3 - 8 : yolk sac

• week 6 - birth: liver

• week 10 - 28: spleen

• after week 18: red bone marrow

site of production after birth

• children: diaphysis of long bones (e.g. femur, tibia)

• adults: mainly plain bones (pelvis, cranium, vertebrae, sternum) & metaphysis of long bones

RBC physiology

nonnucleated biconcave discs

diameter: 7.8 - 8.0 μm³

lifespan: ~120 days

no nucleus or mitochondria → rely on glycolysis → cannot use the O₂ it is carrying

erythropoietin (EPO)

hormone released from the kidney in response to

• hypoxemia

• high altitude

• severe anemia

• decreased O₂ saturation (CO poisoning)

increases RBC survival by inhibiting apoptosis

can be released from renal cell carcinoma & hepatocellular carcinoma

• causes polycythemia vera → suppresses hormone due to increased O₂

Hemoglobin A

The most common hemoglobin type in adults, consisting of two alpha and two beta subunits, crucial for oxygen transport in the blood.

Red Blood Cell Count

Total number of red blood cells in the blood, typically measured in red blood cells per microliter (cells/uL).

Hemoglobin (Hgb)

Concentration of hemoglobin in the blood, usually measured in grams per deciliter (g/dL).

Hematocrit

The volume percentage of red blood cells in the blood. It can be calculated using the mean corpuscular volume (MCV) and red blood cell count.

Mean Corpuscular Volume (MCV)

The average size of red blood cells, measured in femtoliters (fL). It helps differentiate between different types of anemias.

MCHC

Mean corpuscular hemoglobin concentration, which is the average hemoglobin concentration in red blood cells, typically expressed as a percentage.

MCH

Mean corpuscular hemoglobin, referring to the average quantity of hemoglobin present in a single red blood cell, usually measured in picograms per cell (pg/cell).

RDW

Red blood cell distribution width, indicating the variation in red blood cell size. An increased RDW can suggest conditions like anisocytosis.

Extramedullary Hematopoiesis

Production of red blood cells, white blood cells, and platelets outside the bone marrow, often seen in conditions like liver and spleen involvement.

Anemia

A condition characterized by a reduction in the circulating red blood cell mass, leading to decreased hemoglobin, hematocrit, or red blood cell count.

Normocytic Anemia

Anemia with normal-sized RBCs, characterized by reticulocytosis (>2%).

Hemolytic Anemias

Conditions where RBCs are destroyed prematurely, including extravascular and intravascular hemolysis.

Reticulocytes

Immature RBCs released by the bone marrow, used to assess the bone marrow response to anemia.

CBC

Complete Blood Count, which includes WBC, RBC, platelet count, HB, HCT, and RBC indices like MCV, MCHC, and RDW.

Hypoxia Symptoms

Weakness, fatigue, dyspnea, pale skin, headache, lightheadedness, and organ changes due to tissue hypoxia in anemia.

Causes of Anemia

Decreased production, increased loss, or destruction of RBCs due to various factors like iron deficiency, hemolysis, or chronic diseases.

Post-Hemorrhage Anemia

Anemia following acute blood loss, characterized by hypovolemia, hemodilution, and clinical signs of volume loss.

Chronic Hemorrhage

Continuous blood loss exceeding the regenerative capacity of bone marrow, leading to iron deficiency anemia.