Seminar 16

Blood and Hemopoiesis

Bone marrow

Classes 2020/2021

• Plasma is yellowish fluid in which formed elements, organic

compounds and electrolytes are suspended or dissolved.

• During coagulation some organic and inorganic components of the

plasma become integrated in the clot and remaining fluid differs

from plasma (no clot-forming components, straw colored) and is

known as blood serum.

Blood plasma and serum

• Major plasma components:

▪ 92% - water,

▪ 7% - proteins,

▪ 1% - inorganic salts, ions,

nutrients, gases, wastes.

• Plasma leaves vessels and

enters connective tissue spaces

as extracellular fluid.

FORMED ELEMENTS

RED BLOOD CELLS

(ERYTHROCYTES)WHITE BLOOD CELLS

(LEUKOCYES)

PLATELETS

(THROMBOCYTES)

GRANULOCYTES AGRANULOCYTES

• NEUTROPHILIC GRANULOCYTES

(NEUTROPHILS)

• EOSINOPHILIC GRANULOCYTES

(EOSINOPHILS)

• BASOPHILIC GRANULOCYTES

(BASOPHILS)

• MONOCYTES

• LYMPHOCYTES

➢ T

➢ B

➢ NK

Blood cells/µL or mm3

Erythrocytes 4.5-5.5 × 106

Leukocytes 4.0-11.0 × 103

Neutrophils 5000 (55%-65%)

Eosinophils 150 (2%-4%)

Basophils 30 (0.5%- 1.0%)

Lymphocytes 2400 (20-40%)

Monocytes 350 (4-8%)

Platelets approx. 300,000

Normal adult blood volume measures 5 to 6 L.

White blood cells = leukocytes• 1 nucleus, either made by many lobes (granulocytes)

or present as one structure (agranulocytes)

• are round

• 4,000 – 11,000/µl

NEUTROPHILIC

GRANULOCYTES

55-65% EOSINOPHILIC

GRANULOCYTES

2-4%BASOPHILIC

GRANULOCYTES

0,5-1%

LYMPHOCYTES

20-40%

MONOCYTES

4-8%

GRANULOCYTES

AGRANULOCYTES

(containing primary, and specific or

secondary cytoplasmic granules)

(containing only primary =

azurophilic, granules)

• In response to an appropriate stimulus, leukocytes may leave

the bloodstream (diapedesis) and enter the connective tissue

• are responsible for the transport of O2 and CO2

S. Konturek i T. Brzozowski „Fizjologia człowieka”, 2003

A. Stevens „ Histologia”, 2000

• are anucleate

• round, biconcave cells (120 µm2)

• when suspended in an isotonic medium human

erythrocytes are 7.5 µm in diameter, 2.2 µm thick

at the rim, and 0.8 µm thick in the center

• have no organelles

• the biconcave shape provides erythrocytes with a large

surface-to-volume ratio, thus facilitating gas exchange

Red blood cells (erythrocytes)

• mature erythrocytes are filled with hemoglobin and stain

light salmon pink

• erythrocytes with diameters greater than 9 µm are called

macrocytes, and those with diameters less than 6 µm

are called microcytes

• anisocytosis – the presence of a high percentage

of erythrocytes with great variations in size

• The average life span of an RBC is 120 days

• The RBC is quite flexible – a property that permits it to adapt

to the irregular shapes and small diameters of capillaries

• Aged RBCs are fragile and express membrane surface

oligosaccharides that are recognized by splenic, hepatic,

and bone marrow macrophages which destroy those erythrocytes

Red blood cells (erythrocytes)

• Several cytoskeletal proteins (ankyrin, band 4.1 and band 3 proteins,

spectrin, and actin) maintain the shape of RBCs

Junqueira, Basic Histol, 11ed

Inherited alterations in hemoglobin molecules are

responsible for several pathological conditions,

of which sickle cell disease is an example

Sickle cell disease is caused by a mutation

of one nucleotide in the DNA of the gene for

the β-chain of hemoglobin The triplet GAA

(for glutamic acid) is changed to GUA,

which specifies valine.

The sickled erythrocyte is inflexible and

fragile and has a shortened life span that

leads to anemia.

It increases the blood viscosity and can

damage the walls of blood vessels,

promoting blood coagulation.

A. Myśliwski et al. „Atlas histologiczny”, 2002

Leukocytes

MONOCYTE

NEUTROPHIL

EOSINOPHIL

BASOPHIL

LYMPHOCYTE

EOSINOPHIL NEUTROPHIL BASOPHIL

Neutrophils, eosinophils, and basophils have granules that stain specifically

with certain dyes and are called granulocytes. They have a multilobed nucleus.

Underlined cells are presented

under microscopes.

A. Myśliwski et al. „Atlas histologiczny”, 2002

3 types of granulocytes

Neutrophil

Neutrophils have a life span of 6 to 8 hours and

may live for up to 4 days in connective tissue.

Eosinophil

Basophil

Agranulocytes

Junqueira, Basic

Histol, 11ed

A large lymphocyteSmall

lymphocytes

(round dark-

stained nuclei)

A monocyte

(a kidney-shaped nucleus

with delicately stained

chromatin; the cytoplasm

is slightly basophilic)

Lymphocytes and monocytes are considered agranulocytes,

even though they may show azurophilic granules (lysosomes),

which are also present in other leukocytes.

Underlined cells are included

in the practical task.

Lymphocyte

Monocytes

Platelets (thrombocytes)

are small (2 to 4 µm), disk-shaped, anucleated

cell fragments derived from megakaryocytes

• The plasma membrane of a platelet invaginates to form a system

of cytoplasmic channels, called the open canalicular system.

• The central region of the platelet, the granulomere, contains

mitochondria, rough endoplasmic reticulum, the Golgi apparatus,

and granules.

• The periphery of the platelet, the hyalomere, contains

microtubules and microfilaments that regulate platelet shape

and movement.

• Platelets function in blood coagulation by aggregating at lesions

in vessel walls and producing various factors that aid in clot

formation. They are also responsible for clot retraction and

contribute to clot removal.

Platelets

(thrombocytes)

PRACTICAL PART

Peripheral blood

✓ Neutrophilic granulocyte

✓ Eosinophilic granulocyte

✓ Basophilic granulocyte

✓ Lymphocyte

✓ Monocyte

✓ Platelets

Bone marrow blood

Erythropoiesis

✓ Proerythroblast

✓ Basophilic erythroblast

✓ Polichromatophilic erythroblast

✓ Ortochromatophilic erythroblast

✓ Reticulocyte

Granulopoiesis

✓ Myeloblast

✓ Promyelocyte

✓ Neutrophilic myelocyte

✓ Neutrophilic metamyelocyte

✓ Neutrophilic band form

✓ Eosinophilic myelocyte

✓ Eosinophilic metamyelocyte

✓ Eosinophilic band form

Thrombopoiesis

✓ Megakaryocyte

Hemopoiesis

Yolk sac

Liver

Spleen

Bone marrow

In the fetus, hematopoiesis starts during the first trimester

in islands of hematopoiesis found in the yolk sac

(develop from hemangioblasts)

Fetal hematopoiesis continues after the second trimester

in the liver and then in the spleen.

The liver and spleen cease hemopoiesis at about the time of

birth.

During the seventh month of intrauterine life, the

bone marrow becomes the primary site of

hematopoiesis, where it remains during adulthood.

Junqueira, Basic Histol, 11ed

Erythropoiesis

• cell volume decreases

• the continuous increase in hemoglobin

(acidophilic protein) concentration from

proerythroblast to erythrocyte

• a gradual decrease in nuclear volume

• a gradual decrease in the number of

polyribosomes (basophilia decreases)

• an increase in chromatin condensation,

followed by extrusion of a pyknotic

nucleus

• mitochondria and other organelles

gradually disappear

Reticulocytes – the young erythrocytes

• account for 1% to 2% of circulating RBCs

Residual polyribosomes

• anucleated cells

• measure approximately 7 to 8 µm in diameter

• with supravital stains, such as methylene

blue or cresyl blue, a filamentous (reticular)

network of polyribosomes becomes visible

• reticulocytes remain in bone marrow for 1 or 2 days and then are

released into the peripheral blood. Following 1 day of circulation,

reticulocytes mature into erythrocytes.

PROERYTHROBLAST

(PE)

BASOPHILIC

ERYTHROBLAST

(EZ)

POLYCHROMATOPHILIC

ERYTHROBLAST

(EW)

ORTHOCHROMATIC

ERYTHROBLAST

(EK)

RETICULOCYTE

(R)

źródło: A. Myśliwski i wsp. „Atlas histologiczny”, 2002

Erythroid lineage

Underlined cells are included

in the practical task.

Principal processes of granulopoiesis:• modest reduction in cel size

• increasing chromatin condensation and lobation of nucleus

• accumulation of specific granules

• loss of proliferation (cell divisions)

No proliferation

at this and next

stages

Myeloblast Promyelocyte

Neutrophilic

myelocyte

Eosinophilic

myelocyte

Neutrophil

Eosinophil

Basophil

Basophilic

myelocyte

Eosinophilic

metamyelocyte

Neutrophilic

metamyelocyte

Myeloid lineage

Underlined cells are included

in the practical task.

Platelets formationMYELOID STEM CELLS

MEGAKARYOCYTE CFU

(CFU-MK)

MEGAKARYOBLAST

• size 30-50 µm

• a large, ovoid or kidney-

shaped nucleus

• basophilic, nongranular

cytoplasm

PROMEGAKARYOCYTEMEGAKARYOCYTE

• size 40-150 µm

• a large polypoid nucleus that

is highly indented

PLATELETS

źródło: A. Myśliwski i wsp. „Atlas histologiczny”, 2002

• size to 80 µm

• an irregularly shaped

nucleus

Underlined cells are included in the practical task.