HEMATOLOGY, MED II - 3RD YEAR MONONUCLEAR CELLS

- Monocytes
WBC: NON NEOPLASTIC DISORDERS - Lymphocytes
(DR RABO – TRANS by PRETTYVEGANDUGMISSALMONDMILK,
PREPARED by CAYRAPF,
MIDTERMS February 2017) MONOCYTES
 Large cell with abundant cytoplasm often described
as a ground glass cytoplasm
I. Non-neoplastic Disorders  Nuclear material – bean shaped
II. Neoplastic Disorders  Enters the tissue to become highly specialized cells
which we term as MACROPHAGES.
The WBC are composed of :  Different organ systems have own specialized
1. GRANULOCYTES (Neutrophils, Eosinophils, Basophils) macrophages.
- are cells that have distinctive granulations in their  Macrophage are distributed in a so called organ
cytoplasm & they are differentiated by the way which we term as Reticulocyte Endothelial Sytem
they take up (pick up the Wright’s Stain) (Monocyte Phagocytic System)
Romanowsky Stain.  Monocytes are res. for processing antigen & together
2. MONOCYTES & with dendritic cells, they are the major antigen
3. LYMPHOCYTES presenting cells.
 They process antigen & express them so that they
GRANULOCYTES could be recognized by your T Helper Cells →

MED II, HEMATOLOGY - FEBRUARY 2017, 2ND SEMESTER

1. NEUTROPHIL IMMUNE RESPONSE
- Most abundant white cells representing about
60-70% of the whole WBC series. LYMPHOCYTES
- Primarily designed to eliminate pus forming  In the peripheral blood smear, they appear as small
microorganisms cell with high nucleo-cytoplasmic ratio (meaning the
- 1st line of defense nucleus is larger than the cytoplasm), ATYPICAL
- Part of innate immunity (Lymphocytes are part of LYMPHOCYTES → Reactive lymphocytes which have
adaptive) abundant cytoplasm.
2. EOSINOPHIL  Divided into B cell, T cell & NK cells → could not be
- Golden brown granules differentiated by morphology alone
- Responsible for eliminating large parasites  80% of Lymphocytes are T cells (Peripheral Blood
(primarily yung mga Helminths) Smear), 20% are B-cells in the spleen, lymphofollicle,
- Part of the hypersensitivity reaction of the & tonsils.
together with the Basophils o Majority of the lymphocytes are B-cells &
3. BASOPHIL surrounding cells are the T cells.
- Has heavy basophilic granules that obscure the  The white cell parameter includes the Total WBC &
nucleus of the cells differential count, it is very important to remember
- Responsible for Type 1 anaphylaxis that the differential count are merely numeration of
- Also secretes substances that mediate 100 cells ÷ into their diff. morphologic categories =
inflammatory condition once they release 100/diff. morphologic categories
Histamines NORMAL DIFFERENTIAL COUNT
- Histamines act as chemotactic agents, attracting
neutrophils to the site of inflammation Cell type Percent Absolute count
Granulocytes (Neutrophil, Eosinophil, Basophil) are also
Leukocytes 4-11 x 109/L
termed “segmented cells” because the nucleus are
segmented but in the clinics when we say segmenters, Neutrophils 45 - 75% 2.5 - 7.5 x 109/L
we are referring primarily to Neutrophils because the
Eosinophil & Basophil represents less than 1% of the total Stabs 0 - 5%
WBC.
Eosinophils 0 - 5% 0.04 - 0.4 x 109/L

Basophils 0 - 1% 0.01 - 0.1 x109/L

Lymphocytes 10 - 45% 1.5 - 3.5 x 109/L

Monocytes 5 - 10% 0.5 – 1.0 x 109/L

 Automated blood analyzer could diff. granulocytes
 To properly interpret the white cell you must be able
to **** the total white cell count with the diff count in
order to come up with ABSOLUTE VALUES
 It is the absolute count that determines whether you
have Neutropenia, Eosinophilia, Lymphopenia, etc.
(a) Neutrophil (b) Eosinophil (c) Basophill (d) Monocyte (e) Lymphocytes
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 Neutrophils & Monocytes have a common progenitor
cell & both of them are destined to be tissue cells
(They travel from bone marrow & transiently stays in
the peripheral blood → definitely enter tissues which
they engage antigen
 Look for the stages of Neutrophils & Monocyte
maturation!
FORMATION OF NEUTROPHIL & MONOCYTE

MED II, HEMATOLOGY - FEBRUARY 2017, 2ND SEMESTER

NOTES ON THE STAGES:
MONOCYTES
 Eventually become activated to macrophages when
they enter the tissues
 You can only differentiate the different granulocyte STAGES OF GRANULOCYTE MATURATION
at the level of the Myelocytes (when they start to
express the characteristic granules)
 As the Granulocytes mature they express different so
called granules:
o For NEUTROPHIL → the granules are divided
into:
 Primary → Expressed during
PROMYELOCYTIC STAGE  Primary granules ( Azurophilic) granules: HBP, Neutrophil Elastase,
 Secondary Cathepsin G, Protease 3, Azurocidin, Myeloperoxidase
 Secondary granules: Lysozymes, Alkaline Phosphatase,
 Tertiary → Late phase of the Collagenase, Vit B12 binding protein, Lactoferrin
maturation of the cells  Tertiary granules: Gelatinase, Cathepsin B, Cathepsin D, βD-
GRANULOCYTE MATURATION Glucoronidase, α-Mannosidase, Plasminogen activator, MMP-9
 These granules are responsible for the killing effects of
neutrophils (they release those granules to destroy
microorganism)
 The different expression of enzymes → used to
differentiate types of myeloid precursors (the way
they express the diff enzymes)
 Just like the red blood cells, monocytes, lymphocytes
are derived from hematopoietic stem cell.
HEMATOPOETIC GROWH FACTORS

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 The process of granulocyte production just like erythroid cell DISORDER OF GRANULOCYTES & MONOCYTES
production, are influenced by several cytokines acting on  Qualitative
different stages of differentiation. o Chemotaxis (cell mobilization and migration)
o Some are multiple o Phagocytosis
o Some are specific o Killing and digestion
 Multiple effect → They influence maturation of different  Morphologic abnormalities
blood cells  Quantitative
 Specific effect → Granulocytes/Monocyte colony  NOTES:
stimulating factor are responsible for the maturation & o In the clinics, the more common abnormalities we
activation of those cells that are destined to be will find are morphologic abnormalities & the
Granulocytes & Monocytes quantitative abrnomalities
 Some of these cytokines are manufactured using o Qualitative are rare
Recombinant Therapy, some of them have clinical NEUTROPHIL FUNCTION
application
o (ex) Granulocyte Colony Stimulating Factor is used
to rescue people with severe neutropenia
following chemotherapy, sepsis, etc.
 In the bone marrow, most of what we will see under light
microscopy are the so called precursor cells
(morphologically recognizable cells) & very few progenitor
cells
 Most of these cells that are found in the bone marrow are
sort of a storage component.

MED II, HEMATOLOGY - FEBRUARY 2017, 2ND SEMESTER

 The one that circulates or the cells that are found in the
blood/blood vessels are divided into:
o Circulating Neutrophil & Marginating Neutrophil
 Circulating Neutrophil – eto yung
minmeausre pag nagrerequest ng CBC
 Marginating Neutrophil – adherent in the
endothelial cells
NEUTROPHIL KINETICS
CLINICAL APPLICATION OF G-CSF
 Post-chemotherapy, radiotherapy or stem cell
transplantation
 Severe neutropenia
 Severe infection
 Peripheral Blood Stem Cell Harvesting
G-CSF – res. for stimulating granulocyte production
MONOCYTES – RES: DISTRIBUTION OF MONOCYTES
 Neutrophils are derived from the bone marrow, stem cells
then differentiate as neutrophils
 Neutrophils are generally attracted to the site of
inflammation or the site where there are different kinds of
microorganisms by means of diff. chemotactic factors or
chemokines (released by inflammatory cells)
 They enter the circulation & move out of circulation by
means of diapedesis & this process involve diff. lectins (role
in endothelial cells) & this is further augmented by the fact
that during inflammatory response the other inflam. Cells
secretes cytokines (further attract neutrophils to the site of
injury)
 These processes are responsible for the inflammatory response
(rubor, pallor, etc)
↓
Once the neutrophils are near the site of microorganism
↓
They destroy the microorganisms by way of respiratory burst phenomena
↓
Release O2 radicals
Hydrogen Peroxide
↓
Destroy the microorganism
*Sometimes in the process of destroying the microorganisms, they also
destroy the surrounding tissue
NEUTROPHIL FUNCTION

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  Neutrophil phagocytose the microorganism then they form ABSOLUTE NEUTROPHIL COUNT → parameter used to gauge
Lsyozymes defects of chemotherapy. Ito yung binabantayan pag
↓ nagchehemo, <1,000 → DEFER CHEMO
Within that Lysozymes, the respi burst pathway occurs <1000 → RISK FOR INFECTION INCREASE
↓ < 200 → NO INFLA RESPONSE – HYPOTHERMIC → TOXIC
Releasing O2 radicals Hydrogen Peroxide, etc.
↓ CAUSES OF NEUTROPENIA
Destroy microorganisms Selective Neutropenia

MORPHOLOGIC ABNORMALITIES Congenital : Kostmann’s syndrome

Acquired: Drug-induced

Benign (racial or familial)

Cyclical

Immune: autoimmune, SLE, Felty’s syndrome, hypersensitivity

ans anaphylaxis

Large Granular lymphocytic leukemia

Infections: viral, fulminant bacterial infection

MED II, HEMATOLOGY - FEBRUARY 2017, 2ND SEMESTER

Part of general pancytopenia: e.g. BM failure, splenomegaly

 M/C DRUG INDUCED AGRANULOCYTOSIS → ANTI-THYROID

(a) Neutrophil leucocytosis: toxic changes DRUGS (METHIMAZOLE, PTU)
(b) Neutrophil leucocytosis: a Döhle body can be seen in the cytoplasm of the
neutrophil
(c) Megaloblastic anaemia: hypersegmented oversized neutrophil CLINICAL FEATURES OF SEVERE NEUTROPENIA
(d) May–Hegglin anomaly: the neutrophils contain basophilic inclusions 2–5 μm in - associated with infections of mouth and
diameter; there is an associated mild thrombocytopenia with giant platelets
(e) Pelger–Huët anomaly: coarse clumping of the chromatin in pince nez throat : painful ulceration
configuration - skin and anus may be affected
(f) Chédiak–Higashi syndrome: bizarre giant granules in the cytoplasm of a - septicemia
monocyte
(g) Alder’s anomaly: coarse violet granules in the cytoplasm of a neutrophil. *COMMONLY SEEN IN PATIENTS WHO
QUANTITATIVE ABNORMALITIES UNDERGO CHEMOTX ESP FOR ACUTE
1. NEUTROPHILIA LEUKEMIAS
Causes of Neutrophil Leukocytosis

 ASPLENIA – No
spleen either
surgically or due to
repeated infarction
Bacterial infections
EOSINOPHILIA
Inflammation and tissue necrosis
Causes of Eosinophilia
Metabolic disorders
Allergic diseases
Neoplasms
Parasitic diseases
Acute hemorrhage and hemolysis
Recovery from acute infection
Drugs (steroids; lithium; tetracycline)
Certain skin diseases (e.g. psoriasis,
Myeloproliferative disorders etc)

Treatment with myeloid growth factors Drug sensitivity

Polyarteritis nodosa, vasculities,

Rare inherited disorders serum sickness

Asplenia Graft- vs-host disease

Hodgkin’s lymphoma; other tumors

2. NEUTROPENIA
Metastatic malignancy
Absolute Clinical Significance
Neutrophil Count Hypereosinophilic syndrome

>1500/mm3 Normal Chronic eosinophilic leukemia

1000-1500 No significant risk for infection Myeloproliferative diseases

500-1000 Some risk for infection Pulmonary syndromes

<500 Significant risk for infection *EOSINOPHILIA → ABSOLUTE EOSINOPHIL COUNT >500
- NO UNKNOWN CLINICAL SIGNIFICANCE WHEN THERE IS A
<200 Absence of inflammatory response
DECREASE IN EOSINOPHILS. MAS SIGNIFICANT PAG INCREASE.
SAME THING WITH BASOPHILIA.

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 BASOPHILIA
Causes of Basophilia

Chronic myeloproliferative
diseases

Myxedema

Smallpox or chickenpox

Ulcerative colitis

LYMPHOCYTOSIS
Causes of Lymphocytosis

Infections

Thyrotoxicosis

Chronic lymphocytic
leukemia >5000

Acute lymphocytic leukemia

MED II, HEMATOLOGY - FEBRUARY 2017, 2ND SEMESTER

Non-Hodgkin’s lymphoma

MONOCYTOSIS
Causes of Monocytosis

Chronic bacterial infection

Ex. TB

Connective tissue diseases

Protozoan infections

Hodgkin lymphoma, AML and

other malignancies

Chronic myelomonocytic
leukemia

LEUKOERYTHROBLASTIC REACTION
Causes of Leucoerythroblastic
Reaction

Metastatic neoplasm in the marrow

Primary myelofibrosis

Acute and chronic leukemia

Myeloma, lymphoma

Severe megaloblastic anemia

Severe hemolysis

Osteopetrosis

*LEUKOERYTHROBLASTIC REACTION → INCREASE WBC WITH A

SHIFT TO THE LEFT DIFFERENTIAL COUNT (SHIFT TO THE LEFT MEANS
THERE ARE PRESENCE OF IMMATURE CELLS)

*SEEN IN CONDITIONS LIKE MYELOFIBROSIS →

LEUKOERYTHROBLASTIC RXN ARE ACCOMPANIED BY THE
PRESENCE OF A UNIQUE RBC ABNORMALITY WHICH WE CALL AS
TEAR-DROP CELLS

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