GOOD

AFTERNOON

Learning Objectives:
WBC

in health & disease - overview.

Classification
Disorders of WBCs..

Leukopenia:
Neutropenia
Lymphopenia.
Pancytopenia
Leucocytosis:
Neutrophilia
Eosinophilia
Lymphocytosis
Neoplastic disorders (cancer)
Lymphoma
Leukemia (AML/ALL,CML/CLL)

Leukamoid

reactions.

Normal Blood Cells:

Ba
nd

Non-Specific Immunity
Plt

Eosinophil

Specific Immunity

Neutrophil

Lymphocyte

M
on
oc
yt
e

Non granular, Mononuclears

Basophil

Granulocytes, Polymorphs

The blood-forming population of bone marrow is made up of three types of cells:

Self-renewing stem cells

Differentiated progenitor (parent) cells

Functional mature blood cells

All of the blood cell precursors, of the erythrocyte (i.e., red cell), myelocyte (i.e.,
granulocyte or monocyte), lymphocyte (i.e., T lymphocyte and B lymphocyte),
and megakaryocyte (i.e., platelet) series are derived from a small population of
primitive cells called the pluripotent stem cells.

A committed stem cell that forms a specific type of blood cell is called a colonyforming unit (CFU).

Under normal conditions, the numbers and total mass for each type of circulating
blood cell remain relatively constant.

The blood cells are produced in different numbers according to needs and
regulatory factors.

The cytokines that stimulate hematopoiesis are called colonystimulating factors (CSFs), based on their ability to promote the
growth of the hematopoietic cell colonies from bone marrow
precursors.

Lineage-specific CSFs that act on committed progenitor cells include:

erythropoietin (EPO)
granulocyte-monocyte colony-stimulating factor (GM-CSF)
thrombopoietin (TPO)

The major sources of the CSFs are lymphocytes and stromal cells of
the bone marrow.

Other cytokines, such as the interleukins, support the development of

lymphocytes and act synergistically to aid the functions of the CSFs.

White

Blood Cell Count (WBC)

4.1-10.9x103/L
Differential
neutrophils(neu)
lymphocytes (lymp)
monocytes (mono)
eosinophils (eos)
basophils (bas)

60-65%
20-25%
2-12%
0-7%
0-2%

Normal WBC Production:

t
f
i
h
S
t
f
Le

This

increase in leukocytes (primarily neutrophils) is

usually accompanied by a"left shift"in the ratio of
immature to mature neutrophils. The proportion of
immature leukocytes increases due to proliferation and
release of granulocyte and monocyte precursors in the
bone marrow which is stimulated by several products of
inflammation including C3a and G-CSF.
"Right shift"in the ratio of immature to mature
neutrophilsis considered with reduced count or lack of
"young neutrophils" inblood smear, associated with the
presence of "giant neutrophils". This fact shows
suppression of bone marrow activity, as a hematological
sign specific forpernicious anemiaandradiation sickness.

Disorders of white blood cells

The number of leukocytes, or white blood cells, in the

peripheral circulation normally ranges from 4000 to
10,000/L of blood.

The term leukopenia describes an absolute decrease in

white blood cell numbers. The disorder may affect any of
the specific types of white blood cells:
Neutropenia
Lymphopenia

The term leukocytosis describes an absolute increase in in

white blood cell numbers and also may affect any of the
specific types of white blood cells:
Neutrophilia
Eosiniphilia
Basophilia
Lymphocytosis
Monocytosis

Leukopenia:
1. Neutropenia
2. Lymphopenia.
3. Pancytopenia
Leucocytosis:
4. Neutrophilia
5. Eosinophilia
6. Lymphocytosis
7. Lymphadenitis.
. Neoplastic disorders (cancer)
9. Lymphoma
10. Leukemia (AML/ALL,CML/CLL)

WBC Absolute counts in disease:

Penia

Penia

Penia

Penia

Neutro

Philia

Eosino

Philia

Mono

cytosis

Lympho

cytosis

Leukopenia: Neutropenia
Reduction

in granulocytes:

Decreased Production Marrow.

Increased destruction drugs, immune
When

severe Agranulocytosis.

Clinical

features:

Infections chills, fever, fatigue, ulcers .

Neutropenia

Neutropenia refers specifically to a decrease in

neutrophils. It commonly is defined as a circulating
neutrophil count of less than 1500 cells/L.
Agranulocytosis, which denotes a severe neutropenia, is
characterized by a circulating neutrophil count of less than
200 cells/L.
Neutropenia can be:
Acquired
Congenital
Kostmanns syndrome
It occurs sporadically as an autosomal recessive disorder,
causes severe neutropenia while preserving the erythroid
and megakaryocyte cell lineages that result in red blood
cell and platelet production.
The total white blood cell count may be within normal
limits, but the neutrophil count is less than 200/L.
Monocyte and eosinophil levels may be elevated
(compensatory).

Acquired neutropenia

Accelerated removal - removal of neutrophils from the

circulation exceeds production
Inflammation
Infection, viral or bacterial
Increased destruction:
Drug-induced granulocytopenia
Treatment of cancer chemotherapy (e.g., alkylating
agents, antimetabolites)
Irradiation
Autoimmune disorders or drug reactions
May cause increased and premature destruction of
neutrophils
Splenomegaly
Neutrophils may be trapped in the spleen along with other
blood cells
Feltys syndrome
A variant of rheumatoid arthritis, there is increased
destruction of neutrophils in the spleen
Neoplasms involving bone marrow (e.g., leukemias and
lymphomas, myeloma)

Acquired neutropenia

Alcoholism
In states:
Folic acid
Vitamin B12
Iron
Cooper
Aplastic anemia
All of the myeloid stem cells are affected, resulting
in anemia, thrombocytopenia, and agranulocytosis;
Idiopathic neutropenia that occurs in the absence of
other disease or provoking influence.

Leukocytosis: Neutrophilia
Increased

granulocytes:

Acute inflammation, Bacterial infections.

When

severe Leukemoid reaction.

Clinical

features:

Infections or Trauma - fever, fatigue.

Neutrophilia

Physiological:
In newborns
Pregnancy
In labor
Post-partum
After exercise
Drugs or toxics:
Administration of corticosteroids - may increase the release of
neutrophils from the bone marrow and reduce their migration into
tissues;
Acute poisoning with Pb, Hg, some venoms;
Reactive neutrophilia - the result of increased release of neutrophils to
compensate their high affinity for tissues. It is frequently accompanied
by deviation to the left of the leukocyte formula (leukemoid reaction);
Metabolic and endocrine diseases:
Diabetic ketoacidosis
Acute renal failure
Acute gout crise
In some malignant hematologic diseases.