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HEMATOLOGY PRML189 FINALS | A.Y. 2025-2026
HEMATOPOIESIS
Definition
The process of blood cell formation.
Also referred to as hemopoiesis.
Classical marker of hematopoietic stem cells (HSCs): CD34.
CD = clusters of differentiation.
Types of Blood Cells
Red Blood Cells (RBCs)
White Blood Cells (WBCs)
Platelets
RELATED THEORIES (Origin of Hematopoietic Progenitor Cells)
1. Polphyletic Theory
Suggests that all blood cells have their own unique stem cells.
Notes
All blood cells originate from separate stem cells
Separate stem cells for RBC, WBC, megakaryocytes, and platelets
2. Monophyletic Theory
All blood cells are derived from a singular stem cell called a pluripotential stem cell (PSC).
Notes
Most widely accepted theory among experimental hematologists
PHASES OF HEMATOPOIESIS
1. Mesoblastic / Megaloblastic Phase
Chief site of hemopoiesis: yolk sac
First blood cells: primitive erythroblasts (formed during the first 2-8 weeks of life).
Notes
Primitive erythroblasts are the first blood cells produced in human life.
The hemoglobins produced: Portland, Gower 1, and Gower 2.
These hemoglobins deliver oxygen to embryonic tissues and are called embryonic hemoglobins.
2. Hepatic Phase
Chief site of hemopoiesis: fetal liver, with contributions from spleen, thymus, lymph nodes.
Predominant hemoglobin: Hb F (fetal hemoglobin).
Thymus: first fully developed organ in the fetus; major site of T cell production.
Notes
Spleen and lymph nodes also participate in fetal hemopoiesis.
3. Medullary / Myeloid Phase
Chief site of hemopoiesis: bone marrow (BM).
Hematopoiesis starts in the BM cavity before the 5th month of fetal development and becomes the main site by 24 weeks of gestation.
Notes
Bone marrow starts producing blood cells before birth, contrary to common misconceptions.
ADULT HEMATOPOIESIS
Not only occurs in the bone marrow but also in lymph nodes, spleen, thymus, and liver.
Bone marrow can generate (per kilogram of body weight daily):
- 2.5 billion RBCs
- 1 billion granulocytes
- 2.5 billion platelets
Retrogression
The process by which red marrow is replaced by yellow marrow during development, occurring between the ages of 5-7 years.
Notes
Red marrow becomes restricted to the RSVP (Ribs, Sternum, vertebrae, and Pelvis) in adults.
In adults, approximately 50% of marrow is red and 50% is yellow.
Red and Yellow Marrow
Red Marrow: Hematopoietically active.
Yellow Marrow: Hematopoietically inactive, composed of fat cells.
Yellow marrow can revert to active marrow under demand (e.g., blood loss).
LYMPHOID DEVELOPMENT
Primary Lymphoid Organs
Consist of bone marrow and thymus where T and B lymphocytes are derived.
Secondary Lymphoid Organs
Major organs: spleen and lymph nodes
Function of Secondary Lymphoid Organs
Trapping and concentrating foreign substances
Production of antibodies; induction of antigen-specific T lymphocytes.
Spleen
Largest secondary lymphoid organ
Important for immunity via antibody production.
Effects of Splenectomy
In children: increased risk of bacterial sepsis (e.g. S. pneumoniae).
In adults: mild effects similar to children.
RELATED TERMS
Splenectomy
The removal of the spleen.
Splenomegaly
Enlargement of the spleen.
Minor Secondary Lymphoid Organs
Tonsils, appendix, Peyer’s patches, MALT (mucosa-associated lymphoid tissue).
EXTRAMEDULLARY HEMATOPOIESIS
Blood cell production outside bone marrow, mainly in the liver and spleen.
Notes
It occurs under conditions like bone marrow dysfunction or when demand exceeds supply (e.g., hemolytic anemias).
Conditions Leading to Extramedullary Hematopoiesis
Aplastic anemia
Leukemia
Hemolytic anemias
THALASSEMIA
A hematologic disease where the bone marrow attempts to produce more RBCs to counteract severe anemia but remains insufficient.
Extramedullary hematopoiesis may occur in the spleen.
Note: From Rodak’s Hematology
Various test sources and underlying conditions discussed throughout the document.
BONE MARROW COLLECTION SITES
Preferred Sites for Adults:
- P.S. IL. CREST, A.S. IL. CREST, STERNUMPreferred Site for Children (<2 y.o.):
- ANTERIOR MEDIAL SURFACE OF THE TIBIA
BONE MARROW ASPIRATE
Disturbs BM architecture; spread as a smear, stained, examined for disease.
Retained for 10 years due to importance in analysis of individual cell morphology.
M:E (Myeloid-to-Erythroid) Ratio
Proportion of myeloid cells to nucleated erythroid precursors in the bone marrow aspirate.
Notes
In healthy adults, the M:E ratio varies from roughly 1.5:1 to 3.3:1.
In leukemia, the M:E ratio is approximately 10:1.
HEMATOPOIESIS
Continues into adulthood with contribution from lymph nodes, spleen, thymus, and liver (in pathological instances).
RETICULOCYTES
Immature red blood cells produced in bone marrow, indicating active erythropoiesis.
MATURATION STAGE OF RBCS
Stages: Rubriblast, Prorubricyte, Rubricyte, Metarubricyte, Reticulocyte, Mature erythrocyte.
Features
Red cell size, nucleus characteristics, presence of nucleoli, cytoplasmic change during maturation noted.
SUPERVITAL STAINS
Used to stain reticulocytes; examples include Brilliant Cresyl Blue and New Methylene Blue.
HORMONES RELATED TO ERYTHROPOIESIS
Erythropoietin (EPO)
Growth Hormone (GH)
Testosterone
Prolactin
Estrogen
Erythropoietin Functionality
Stimulates release of reticulocytes and maturation in BM; secreted by kidneys.
Erythropoiesis Pathway
Involvement of BFU-E, CFU-E, differentiating into recognizable precursors, eventually into mature erythrocytes.
ANEMIAS
Definition
Decrease in RBC, hemoglobin, or hematocrit below normal levels.
Anemia is a manifestation, NOT a disease.
CLASSIFICATION OF ANEMIAS
Morphologic Classification:
1. Normocytic, Normochromic
2. Microcytic, Hypochromic
3. Macrocytic, Normochromic
Examples of Microcytic Anemia:
Iron deficiency and Thalassemia; causes include chronic blood loss, malabsorption.
Megaloblastic Anemia Classification:
Caused by Vitamin B12 or Folate deficiency.