The white cells 1: granulocy - PowerPoint Presentation

Slide1

The white cells 1: granulocy es,monocytes and their benigndisorders

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The white blood cells (leucocytes) may be divided into two broad groups:1-the phagocytes Granulocytes, which include three

types of cell-

neutrophils

(polymorphs),

eosinophils

and

basophils

-together with

monocytes

comprise the phagocyte

2-immunocytes

Note : Only

mature

phagocytic

cells and lymphocytes are found in

normal peripheral blood

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GranulopoiesisThe blood granulocytes and monocytes are formedin the bone marrow from a common precursor cell

In the

granulopoietic

series progenitor

cells which are:

myeloblasts

,

promyelocytes

and

myelocytes

form a

proliferative or mitotic pool

of cells

while

the

metamyelocytes

, band and segmented granulocytes

make up

a post-mitotic maturation

compartment

Large

numbers of band and segmented

neutrophils

are held in the marrow as a

'reserve

pool' or storage

compartment

.

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In the bone marrow

normally

contains more myeloid cells than

erythroid

cells in the ratio of 2 : 1 to 12 :

1

the

largest proportion

being

neutrophils

and

metamyelocytes

.

In the stable or normal state, the bone

marrow storage

compartment contains 10-15 times

the number

of granulocytes

found

in the

peripheral blood

.

Following

their release from the bone marrow,

granulocytes spend only 6-10 h in the circulation

before moving into the tissues where they

perform their

phagocytic

function

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In the blood stream

there

are two pools usually of about equal

size

:

the

circulating pool

(included in the

blood count

)

and

the

marginating

pool

(not included in

the blood count).

It

has been estimated that they

spend on average 4-5 days in the tissues before they

are destroyed during defensive action or as the

result of senescence.

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Control of granulopoiesis: myeloid growth factors

Many growth factors are involved in this

maturation process including

:

interleukin-1

(IL-1

)

IL-3

IL-5 (for

eosinophils

),

IL-6

IL-11

granulocytemacrophage

colony stimulating

factor (GM-CSF

)

granulocyte

CSF (G-CSF)

monocyte

CSF (MCSF

)

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Function of growth factors The growth factors stimulate proliferation and

differentiation

and also affect

the

function

of the mature cells on which they act

e.g.

Increased granulocyte and

monocyte

production in

response to an infection is induced by

increased production

of growth factors from

stromal

cells

and T

lymphocytes, stimulated by

endotoxin

, IL-1

or

tumour

necrosis factor (TNF)

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The normal function of neutrophils and

monocytes

may

be divided into

three phases:

Chemotaxis

(cell mobilization and migration)

The

phagocyte

is attracted to bacteria or the site

of inflammation

by

chemotactic

substances.

Phagocytosis

The foreign material (e.g. bacteria,

fungi

) or dead or damaged cells of the host are

Phagocytosed

Killing and digestion

This occurs by

oxygen dependentand oxygen-independent pathways.

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Functional Disorders of Phagocytic Leucocytes12

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Disorders characterised by neutrophil dysfunction

1. Impaired adhesion:

Congenital leucocyte adherence deficiency (Deficiency of CD11/CD18 surface glycoproteins)

Drugs: corticosteroids, alcohol

2. Impaired motility:

Hyperimmunoglobulin

E syndrome

Chediak

-Higashi syndrome

Diabetes mellitus, Hodgkin’s disease, leprosy

3. Impaired

microbicidal

killing:

Chronic granulomatous disease

Myeloperoxidase deficiency

Chediak

-Higashi syndrome

Leukaemias

13

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Benign disordersof granulocyte morphology

1-Pelger-Huet

anomaly

In this

uncommon condition

bilobed

neutrophils

are found in the peripheral

blood. Occasional

unsegmented

neutrophils

are also seen.

Inheritance is

autosomal

dominant.

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2-May-Hegglin anomaly In this rare condition the

neutrophils

contain basophilic inclusions of RNA

in

the cytoplasm

.

There is

an associated mild thrombocytopenia with

giant platelets

.

Inheritance

is

autosomal

dominant.

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3-The Chediak-Higashi syndrome is inherited

in an

autosomal

recessive

manner,

and there are

giant granules in the

neutrophils

,

eosinophils,monocytes

and lymphocytes accompanied by

neutropenia

, thrombocytopenia

and

marked

hepatosplenomegaly

.

disorders may be associated with severe

disease.

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Common morphological abnormalities

Hypersegmented

forms occur in

megaloblastic

Anaemia

Dahle

bodies and toxic changes

in infection.

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The 'drumstick' appears on the nucleus ofa proportion of the neutrophils in normal females

and is caused by the presence of two X chromosomes.

Pelger

cells

are seen in the benign congenital

abnormality but also in patients with acute myeloid

leukaemia

or

myelodysplasia

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Shift to the left:

increase in the number of band forms and the occasional presence of more primitive cells in the peripheral blood.

Leukoerythroblastic

picture:

a presence of a shift to left plus nucleated RBC in the peripheral blood.

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Causes of leucoerythroblasticblood film

Metastatic neoplasm in the marrow

Primary

myelofi

brosis

Acute

and

chronic

myeloid

leukaemia

Myeloma, lymphoma

Miliary

tuberculosis

Severe

megaloblastic

anaemia

Severe

hemolysis

Osteopetrosis

22

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Causes of leucoerythroblasticblood film

Metastatic neoplasm in the marrow

Primary

myelofi

brosis

Acute

and

chronic

myeloid

leukaemia

Myeloma, lymphoma

Miliary

tuberculosis

Severe

megaloblastic

anaemia

Severe

hemolysis

Osteopetrosis

23

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The Leukomoid Reaction

a

reactive excessive leukocytosis with the presence

of immature cells (

myeloblasts

,

promyelocytes

and

myelocyte

) in the peripheral blood.

In

other words (

leukocytosis + left shift

)

. Usually

it is a neutrophil leukocytosis

. It can be lymphoid

Causes :

Severe infection

Severe

haemolysis

Metastatic cancer

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