CLINICAL HEMATOLOGY PROFESSOR HANDOUTS

COLLEGE OF MEDICAL LABORATORY SCIENCE

CELLS
- are the structural units that constitute living organisms.

Organelle Location Appearance and Size Function

Plasma Membrane Outer boundary of cell Lipid bilayer consisting of
phospholipids, cholesterol,
protein, glycolipids and
glycoproteins from a
glycocalyx
Nucleus Within cell Round/oval; varies in
diameter; DNA and proteins
Nucleolus Within nucleus Usually round or irregular
shape
Ribosomes Free in cytoplasm and on Macromolecular complex
outer surface of the composed of protein and
Rough ER ribosomal RNA
Rough Endoplasmic Membranous network Branching, membrane-lined
Reticulum throughout cytoplasm tubules and sacs; studded
with ribosomes on outer
surface
Smooth ER Membranous network Membrane-line tubules
throughout the lacking ribosomes;
cytoplasm continuous with rough ER
Provides physical barrier
for cell; facilitates and
restricts interchange of
substances with
environment
Controls cell division and
function. Contains DNA
and RNA
Synthesizes ribosomal
RNA and assembles
ribosomes subunits
Synthesizes Protein
Synthesiszes membrane-
bound and secreted
proteins
Synthesizes
phospholipids and
steroids; detoxifies drugs
and stores calcium
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Golgi Apparatus/Complex Next to nucleus and System of stacked,
rough ER membrane-bound, flattened
sacs
Mitochondira Randomly distributed in Elliptical/oval structures
cytoplasm surrounded by inner and
outer membranes
Lysosomes Randomly distributed in Membrane-bound sacs
cytoplasm
Microfilaments Near nuclear envelope, Double-stranded,
plasma membrane, and intertwined solid structures
mitotic processes of actin
Intermediate Filaments Cytoskeleton Solid structures 8-10 nm in
diameter, seld-assemble into
large bundles
Microtubules Cytoskeleton and Hollow cylinder 25nn in
centrioles near nucleus diameter, consists of 13
protofilaments form from a-
ad b- tubulin
Centrosomes Near nucleus Composed of 2 cylinder-
shaped centrioles, each with
nine sets of triplet
microtubules; centrioles
oriented at right angles to
each other
Modifies and packages
macromolecules for
other organelles and for
secretion
Power house of the cell.
Produces most of the
ATP for the cell
Contains hydrolytic
enzymes that grade
unwanted material in the
cell
Supports cytoskeleton
and motility
Provides strong
structural support
Maintains cell shape;
involved in cell and
organelle motility and
mitotic process
Contains centrioles that
serve as insertion points
for mitotic spindle fibers

Hematopoietic Microenvironment

- Hematopoiesis occurs predominantly in the Bone

Marrow from third trimester of fetal life through
adulthood

Cell Cycle

Stages

1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase
6. Cytokinesis/Interphase
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Mitosis: the process by which a cell replicates its chromosomes and then segregates them, producing two
identical nuclei in preparation for cell division. Mitosis is generally followed by equal division of the cell's
content into two daughter cells that have identical genomes

Meiosis: a type of cell division in sexually reproducing organisms that reduces the number of chromosomes in
gametes

Cell Death by Necrosis and Apoptosis

- Necrosis is a pathologic process caused by direct external injury to cells such as, from burns, radiation, or
toxins.

- Apoptosis is a self-inflicted cell death originating from the activation signals within the cell itself

HEMATOPOIESIS

Hematopoiesis
 Is also known as hemopoiesis
 Is a continuous, regulated process of blood cell production
o Cell renewal,
o Cell proliferation,
o Cell differentiation
o Cell maturation
 The processes lead to the formation, development, and specialization of all of the
functional blood cells that are released from the bone marrow to the blood
circulation.
o Adults: restricted to the bone marrow
o Fetal Development : occurs in different areas of the developing fetus
 Mesoblastic phase
 Hepatic phase
 Medullary phase

Hematopoiesis
• Erthropoiesis
• Leukopoiesis
• Granulocpoiesis
• Monopoiesis
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

• Lymphopoiesis
• Megakaryopoiesis
• Thrombopoiesis

Hematopoietic Tissues

 Organs involved in blood productions.

 Medullary hematopoiesis
o Involves the formation of normal blood cell in the marrow

o Vertebrae, ribs, sternum, pelvis, skull, scapulae, proximal end of the long bones

*** occurs in the bone marrow bounded by sinusoids

 Extramedullary hematopoiesis
o Involves the formation of blood cells outside the bone marrow.

o Spleen, liver, lymph nodes, areas of lymphatic tissues

Bone Marrow

 Produces RBC, Platelets, granulocytes

 Also serves as one of the formation sites of lymphocytes, monocytes and plasmacytes

Yellow Bone Marrow

 Filled with fat

 The fat occupies reserve space and mixes with the solution and disappears as the blood cells
increases
--------→ for regeneration to occur on demand without interfering with the
vital structure.
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Pre-Natal Hematopoiesis
Mesoblastic Phase/Yolk Sac Phase

 begins around the 14th-19th day of embryologic development after fertilization

 High demand of the fetus for Oxygen--→ Occurs in the yolk sac (mesenchymal cells)

 Characterized by the development of primitive erythroblasts that produce measurable

embryonic hemoglobin and nucleated.

 No leukocytes and thrombocytes at this phase

 Does not contribute significantly to definitive hematopoiesis

 Occurs intravascularly (within a developing vessels)

 -blood cells in the yolk sac originate in angiogenic cell clusters ("blood islands")
Hepatic Phase

 begins at 4th to 5th gestational week

 Is characterized by recognizable clusters of developing erythroblasts, granulocytes and

monocytes ; Production of megakaryocytes also begins at this phase

 Liver : the chief site of hematopoiesis ( Peak : by the third month→ and retaining activity
until 1-2 weeks after birth

 Spleen, kidney, thymus and lymph nodes contribute to the process.

 Thymus - T cell production
 Kidney and spleen – B cell production
 Lymph nodes – produces RBC, granulocytes, megakaryocytes

*** developing erythroblasts signal the beginning of definitive hematopoiesis ( with decline in
primitive hematopoiesis of the yolk sac)

 Lymphoid cells begin to appear.

 Occurs extravascularly

 Detectable levels of hemoglobin (Hb) F, HbA and HbA2 may be present

CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Medullary Phase / Myeloid Phase

 Starts in the 5th month of gestation

 Occurs in the developing medulla bone marrow cavity.

 Mesenchymal cells (embryonic cells)--→ core of the bone and differentiate into skeletal
cells
and hematopoietic blood cells

 Myeloid activity starts in this stage

 Myeloid-Erythroid Ratio approaches the adult level of 3:1 by 21 weeks of gestation.

 On the 6th month : Bone marrow is the primary site of hematopoiesis

 Erythropoeitin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte

colony-stimulating factor (GM-CSF), fetal hemoglobin (HbF), HbA2 and adult hemoglobin can
be detected.

Post-Natal Hematopoiesis

 Newborn : 80-90% of bone marrow is active in producing Nucleated RBCs, Lymphocytes and
hemoglobin.
 Young Adult (Around 20y.o.) 60% of bone marrow is active
 Older Adult (aroung 55 y.o.) : 60% yellow marrow and 40% red marrow.

Bone Marrow

RED BONE MARROW – is composed of extravascular cords that contain all the developing blood cell
lineages stem and progenitor cell, adventitial cells and macrophages.

Main Function : production and proliferation of blood cells that are divided into three
compartments/cell types (Stem cells, Progenitor cells and Precursor cells)
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Liver

- hepatocytes have many functions, including protein synthesis and degradation, coagulation factor synthesis,
carbohydrate and lipid metabolism, drug and toxin clearance, iron recycling and storage, and hemoglobin
degradation, in which bilirubin is conjugated and transported to the small intestine for eventual excretion.

- Kupffer cells are macrophages that remove senescent cells and foreign debris from the blood that circulates
through the liver

- liver can maintain hematopoietic stem and progenitor cells to produce various blood cells (called
extramedullary hemato poiesis) as a response to infectious agents or in pathologic myelofibrosis of the bone
marrow

Spleen

- largest lymphoid organ

- exterior surface of the spleen is surrounded by a layer of peritoneum covering a connective tissue capsule

3 types of splenic tissue:

1. White pulp
2. Red pulp
3. Marginal zone

Lymph nodes

- organs of the lymphatic system located along the lymphatic capillaries that are parallel to the circulatory
system.

Thymus

- T-cells

Cell Compartments/Types

1. Stem cells (Pluripotential or Multipotential cells) – differentiate into specific cell lines. Stem
cells differentiates colony forming units (CFU) ; the differentiate into either of pathways :

- Giving rise to the primitive B or T lymphocytes

- Giving rise to erythrocytes, granulocytes and megakaryocytes (thrombocytes)
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

2. Progenitor cells (Unipotential stem

cells) – differentiate only into a single cell
line. These cells develop into BFU-E, CFU-E, CFU-MEG, CFU-GM
3. Precursor cells – these cells mature into blast forms (myeloblasts, megarkayoblasts,
pronomoblast, and lymphoblast)

Bone Marrow Cell Production

Bone marrow evaluation is based on Myeloid-Erythroid Ratio (M:E Ratio)

Normal M:E ratio - 3-4 :1
Most cell production in the bone marrow is myelocytic and is mostly granulocytic
*** Myelocytic pool of cells takes 3 days to develop into mature cells-------> peripheral blood

Cell Proliferation and Differentiation

All blood cells originated from Pluripotent stem cell (PPSC)

Differentiation is determined by Protein Factors and influence by Growth Factors

Growth factors are regulatory glycoprotein hormones e.g. Erythropoetin, interleukin, and colony
stimulating factors

Cell Proliferation and Differentiation

o Hematopoietic stem cells develop into colony-forming units- → Granulocytes,
Erythrocytes, Monocytes and Megakaryocytes (CFU-GEMM)

 The CFU-GEMM differentiates into the following in the peripheral blood:

• BFU-F -----→ CFU-E -→ Erythrocytes

• CFU-MEG -------------------→ Thrombocytes
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

• CFU-GM ----→ CFU-M ---→ Monocytes

• CFU-GM ---→ CFU –G ---→ Segmented Neutrophils

• CFU-EO-------------------→ Eosinophils

Basic Blood Cell Morphology

Nucleus

 With heterochromatin that does not undergo cell division (Dark and clump

 Also contains euchromatin – undergoes cell division. (light, loose, and with nucleoli)
CLINICAL HEMATOLOGY PROFESSOR HANDOUTS
COLLEGE OF MEDICAL LABORATORY SCIENCE

Cytoplasm

 Contains cellular organelles that stain according to their contents

• Blue indicates components that are rich in RNA

Cell Characteristics

Immature Cells

 High N:C ratio

 Nucleoli present

 Chromatin is loose and light

 Cells are not segmented

 Cytoplasm is intensely blue

 Organelles are not define

Mature cells

 Low N:C ratio

 No nucleoli

 Chromatin is dark and

clumped

 Cell are segmented

 Cytoplasm is moderately blue

 Organelles are defined

Cytokines and Growth Factors

- group of specific glycoproteins call

hematopoietic growth factors or cytokines