White Blood Cells

Disorders
Presented by Group 5
Rutba
Khunsa
Khizar
Tehreem
Noor Fatima
Asif
Aezea
Tayyaba

Presented To
DR.UMER ARSHAD
 Table of contents

01 02 03
Granulocytes Granulopoieses
Growth Factors

04 05 06
Disorders of neutrophil Causes of monocytosis
and monocyte Neutropenia Eosinophil and
function basophilia
 Table of contents

07 08
Histiocytic and Lysosomal
dendritic cell disorder storage disease
Here is where your presentation begins
 01
Granulocytes
Introduction Of WBC
White blood cells (WBCs), also known as
leukocytes, are crucial components of the
immune system that help defend the
body against infections and foreign
substances. They are produced in the
bone marrow and found in the blood and
lymphatic system. There are several
types of WBCs, each with specific
functions:
Types and Function
White blood cells (WBCs) come in several types, each with distinct functions:

1.Neutrophils : These are the most abundant WBCs and are crucial for
fighting bacterial infections. They ingest and digest microorganisms through a
process called phagocytosis.
2.Lymphocytes : This group includes:
● T cells: They regulate immune responses and directly kill infected cells.
● B cells: They produce antibodies that bind to specific antigens on pathogens,
marking them for destruction.
● Natural Killer (NK) cells*: They destroy virus-infected cells and tumors.
3. Monocytes: These cells differentiate into macrophages and dendritic cells
when they enter tissues. Macrophages engulf and destroy pathogens and
dead cells, while dendritic cells present antigens to T cells
Types and Function
4. Eosinophils : They are involved in combating parasitic infections and
modulating allergic responses by attacking parasites and regulating
inflammation
5. Basophils : These cells release histamine and other chemicals during
allergic reactions and inflammation, contributing to the immune response.

Each type plays a specific role in maintaining the body’s defense mechanisms
and ensuring a balanced immune response.
Neutrophil Precursors
 02
Granulopoiesis
 Granulopoiesis
Granulopoiesis is the process of producing granulocytes, a type of white blood cell
characterized by the presence of granules in their cytoplasm. This process occurs in
the bone marrow and involves several stages:

1. Myeloblast: The earliest precursor cell in granulopoiesis.

2. Promyelocyte: The cell begins to develop granules in its cytoplasm.

3. Myelocyte: Granules mature and the cell starts to take on the characteristics of
a specific granulocyte type (neutrophil, eosinophil, or basophil).

4. Metamyelocyte: The cell's nucleus starts to condense and change shape.

Granulopoiesis
5. Band cell: The nucleus elongates into a band-like shape,
and the cell is nearly mature.

6. Mature granulocyte: The final stage, where the cell is

fully developed and ready to enter the bloodstream to
perform its immune functions.

Granulopoiesis is crucial for maintaining adequate levels of

granulocytes in the blood, which are essential for responding
to infections and inflammation.
 03
Growth Factors
Growth Factors
Myeloid growth factors are proteins that stimulate the production and differentiation of
myeloid cells, which include granulocytes (such as neutrophils, eosinophils, and
basophils) and monocytes. Key myeloid growth factors include:

1. Granulocyte Colony-Stimulating Factor (G-CSF): Stimulates the production

and release of neutrophils from the bone marrow.

2. Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): Promotes

the production of both granulocytes and macrophages

3. Macrophage Colony-Stimulating Factor (M-CSF): Enhances the production

and function of macrophages.

These factors are crucial for maintaining adequate levels of myeloid cells, especially
during infections or after chemotherapy.
 04

Disorders of neutrophil and monocyte

function
Impaired Chemotaxis

 Phagocytes fail to migrate to the site of infection These

defects occur in rare congenital abnormalities (e.g lazy
leucocyte syndrome)
 More common acquired abnormalities, either of the
environment (e.g corticosteroids therapy of the
leucocytes in acute or chronic myeloid leukemia)
Reduced Phagocytosis

 Phagocytes can't engulf and ingest pathogens

these defects arise because of lack of
opsonization which may be caused by
congenital or acquired of
hypogammaglobulinemia or lack of
complement components
Defective Intracellular Killing

 Phagocytes can't kill ingested pathogens This abnormality is clearly

illustrated by the rare X-linked or autosomal recessive chronic
granulomatous disease that results abnormal leucocyte oxidative
metabolism

 Other rare congenital abnormalities may also result in defects of bacterial

killing (e.g myeloperoxidase deficiency)

 Acute or chronic myeloid leukemia myelodysplasia syndrome may also be

associated with defective killing of ingested microorganisms.
Benign Disorders Overview

 Definition: Non-cancerous conditions with a

generally good prognosis.
 Characteristics: Mild, manageable, and
typically not life-threatening.
Pelger-Huet Anomaly:

 Definition: Genetic disorder with hypo

segmented neutrophils.
 Features: Two- lobed neutrophils, often
asymptomatic.
 Inheritance: Autosomal dominant.
May-Hegglin Anomaly:

 Definition: Blood disorder with large granules in

white blood cells.
 Features: Large platelets, mild
thrombocytopenia, and inclusions in white cells.
 Inheritance: Autosomal dominant.
Other Rare Disorders and Morphological
Abnormalities:
Other Rare Disorders

Examples include:

 Chédiak-Higashi Syndrome
 Generally benign but may require monitoring and Hurler's
Syndrome.
Other Rare Disorders and Morphological
Abnormalities:
Common Morphological Abnormalities:

Anisocytosis: Variation in red blood cell size.

Poikilocytosis: Variation in red blood cell shape.
Hypersegmented Neutrophils: Linked to megaloblastic
anemia.
Neutrophil Leukocytosis Overview

Definition: Elevated neutrophil count in the blood.

Causes: Infections: Bacterial or viral.
Inflammation: Acute or chronic.
Stress: Physical or emotional.
Medications: Corticosteroids or other drugs.
Leukemoid Reaction

Definition: High white blood cell count resembling

leukemia, but non-cancerous.
Causes: Severe infections, toxins, hemorrhage.
Features: Elevated white blood cells with
immature granulocytes.
Leukoerythroblastic Reaction

Definition: Presence of immature white blood

cells and red blood cell precursors in blood.
Causes: Bone marrow disorders, metastatic
cancer, severe anemia.
Features: Immature neutrophils and erythroblasts
in peripheral blood.
Pelger huet Neutrophil May heglin
anomaly leukocytosis anomaly
 05
Neutropenia
Neutropenia
Neutropenia refers to lower-than-normal levels of neutrophils in your
blood.

Neutrophils Normal Range : 2,500 _7,000 neutrophils per

microliter.
Mild neutropenia: 1000 to 1500/mcL
Moderate neutropenia: 500 to 1000/mcL
Severe neutropenia: <500/mcL
• Cancer
What causes neutropenia?
• Autoimmune deficiencies.
• Genetic conditions
• Infections
• Medications
Benign ethnic neutropenia (BEN)

is a chronic (long-lasting) congenital (present from birth)

form of neutropenia that’s most common in people of
African, Middle Eastern and West Indian. having an
absolute neutrophil count (ANC) <1500 cells/μL with no
increased risk of infection.

Cause : By a polymorphism in the Duffy antigen receptor

for chemokines (DARC)
Congenital Neutropenia.
(Kostmanns syndrome)
● Present in first year of life with life threaten infection
inherited disorder autosomally recessive

Cause by: mutation of gene ELA2 coding for neutophil

elastase
Cyclic Neutropenia

● Cyclic neutropenia is a rare blood disorder characterized by

regular fluctuations in the number of neutrophils.
● These fluctuations occur in a cyclical pattern, with periods
of extremely low neutrophil counts (neutropenia) followed
by periods of normal levels
● Increased infection risk: Low neutrophil levels make
individuals susceptible to infections.
● Symptoms: Fever, fatigue, mouth sores
Autoimmune Neutropenia (AIN)

Autoimmune Neutropenia (AIN) is a blood

disorder where the body’s immune system
mistakenly attacks and destroys neutrophils.
● Cause: The immune system malfunctions and
attacks its own neutrophils.
● Symptoms: Often no symptoms, but can include
frequent infections.
Idiopathic Benign Neutropenia

Idiopathic benign neutropenia is a condition where a person

has a lower than normal number of neutrophils) in their blood
for no apparent reason.
Clinical Features

● Fever: This is often the first and most important sign of

infection in neutropenic patients.
● Fatigue: General weakness and tiredness.
● Sore throat (pharyngitis): Pain or discomfort when
swallowing.
● Swollen lymph nodes: Enlarged lymph nodes in the neck,
armpits, or groin.
● Mouth ulcers: Painful sores in the mouth.
● Skin infections: Redness, swelling, and pain in the skin.
Diagnosis:

● Bone Marrow Examination

● Marrow aspiration
● Trephine biopsy

Management:

1. Supportive care:

● Monitor blood counts and adjust treatment accordingly

● Provide anti-infective prophylaxis (e.g., antibiotics, antifungals)
● Use growth factors (e.g., G-CSF, GM-CSF) to stimulate neutrophil
production
2. Medications:
● Antibiotics for bacterial infections
● Antifungals for fungal infections
● Antivirals for viral infections
● Granulocyte-colony stimulating factor (G-CSF) to stimulate
neutrophil production

3. Corticosteroid therapy
 06

Causes of monocytosis
Eosinophil and basophilia
Monocytosis, Eosinophilia, and
Basophilia Overview

● Monocytosis, eosinophilia, and basophilia indicate increased

counts of monocytes, eosinophils, and basophils,
respectively. These conditions are often associated with
underlying pathologies, including infections, inflammatory
conditions, or hematologic disorders.
Monocytosis

 Definition: Monocytosis is an elevated monocyte

count, typically greater than 0.8 x 10^9/L in adults.
 Function of Monocytes: Monocytes differentiate
into macrophages and dendritic cells, playing a key
role in phagocytosis and immune regulation. They
are essential for tissue repair, immune surveillance,
and responding to infections and inflammation.
Causes of Monocytosis.
1. Chronic Infections: Tuberculosis, bacterial endocarditis - Chronic
parasitic (e.g., malaria) and fungal infections (e.g., histoplasmosis)

2. Inflammatory Conditions: Sarcoidosis Inflammatory bowel disease

3. Malignancies: Chronic myelomonocytic leukemia (CMML) - Acute

monocytic leukemia

4. Recovery from Acute Infections: Transient monocytosis can occur

during recovery from infections like sepsis or severe neutropenia.
sarcoidosis inflammatory Chronic myelomonocytic Acute Monocytic
bowel disease leukemia leukemia
 Eosinophilia

 Definition: Eosinophilia refers to an increased eosinophil

count above 0.5 x 10^9/L in the blood.

 Function of Eosinophils: Eosinophils are involved in

combating multicellular parasites, allergic reactions, and
modulating the inflammatory response by releasing
cytotoxic granules.
Causes of Eosinophilia

1. Allergic Disorders: Asthma, allergic rhinitis, atopic dermatitis Drug-

induced eosinophilia due to hypersensitivity reactions

2. Parasitic Infections: Helminthic infections Protozoal infections (less

common)

3. Autoimmune and Inflammatory Disorders: Eosinophilic

granulomatosis with polyangiitis (EGPA) Systemic lupus erythematosus
(SLE)

4. Hematologic Malignancies: Hodgkin’s lymphoma

5. Other Causes: Hyper eosinophilic syndrome (HES)

 Atopic
Dermatitis
Hodgkin’s lymphoma Hyper eosinophilic syndrome (HES)
 Basophilia

 Definition: Basophilia is an increase in basophil count,

typically greater than 0.1 x 10^9/L in the blood.

 Function of Basophils: Basophils are involved in

hypersensitivity reactions by releasing histamine and
leukotrienes, contributing to immune responses against
parasitic infections.
Causes of Basophilia

1. Myeloproliferative Disorders: Chronic myeloid leukemia (CML),

Polycythemia vera, essential thrombocythemia.

2. Chronic Inflammatory Conditions: Ulcerative colitis, rheumatoid

arthritis.

3. Endocrine Disorders: Chronic hypothyroidism.

4. Infections and Hypersensitivity: Viral infections (e.g. varicella,

smallpox) Allergic dermatitis.

5. Other Causes: Post-splenectomy state, Iron deficiency.

NOTE :
 Monocytosis, eosinophilia, and basophilia are markers of
underlying chronic infections, inflammatory diseases, or
hematologic disorders. Accurate identification of the cause
is crucial for diagnosis and management.
 07

Histiocytic and dendritic cell disorders

Histiocytic and dendritic cell
disorders
● Histiocytic and dendritic cell disorders can be
classified into various categories based on their
clinical, histological, and molecular features
Histiocytic Disorders:
Langerhans Cell Histiocytosis (LCH):

Single-System LCH:
Bone LCH (Eosinophilic Granuloma): Typically affects a single bone.

Skin LCH: May present as skin lesions, including the classical “birbeck granules” on electron microscopy.

Multisystem LCH:
Hand-Schuller-Christian Disease: Involves multiple bones, skin, and sometimes the pituitary gland.

Letterer-Siwe Disease: A more aggressive form that involves multiple systems, including the liver,
spleen, and bone marrow.
● 2. LCH may affect any organ of the body, but those more
frequently affected in children are the bones (80% of cases),
skin (33%) , and the pituitary gland (25%), liver, spleen,
hematopoietic system or lungs (15% each) , lymph nodes (5%-
10%), or the central nervous system (CNS) (2%-4% excluding
the pituitary).In adults, lung involvement is more frequent than
in children.
Non-Langerhans Cell Histiocytosis:

1.Hemophagocytic Lymphohistiocytosis (HLH):Can be

primary (genetic) or secondary (triggered by infections,
malignancies, or autoimmune diseases). Characterized by
excessive activation of histiocytes and macrophages, leading to
severe systemic inflammation.
2.Rosai-Dorfman Disease (Sinus Histiocytosis with Massive
Lymphadenopathy): Characterized by sinusoidal proliferation
of histiocytes, typically presenting with massive
lymphadenopathy.
3.Systemic Histiocytosis (e.g., Erdheim-Chester Disease):
Rare condition involving histiocyte infiltration in multiple organs,
including bone, skin, and organs such as the heart or lungs.
 Dendritic Cell Disorders:
1. Dendritic Cell Neoplasms:

● Follicular Dendritic Cell Sarcoma: Originates from follicular dendritic cells in lymph nodes and
can present with masses in lymph nodes or other organs. Interdigitating Dendritic Cell Sarcoma:
Rare cancer arising from interdigitating dendritic cells, often presenting in lymph nodes or as
disseminated disease.
● Plasmacytoid Dendritic Cell Neoplasms: Includes plasmacytoid dendritic cell neoplasms, which
can present as tumors or leukemias.

2. Dendritic Cell Activation Disorders:

Hyper-IgE Syndrome: Can be associated with abnormal dendritic cell function, leading to recurrent
infections and other clinical manifestations.

The classification of these disorders helps guide diagnosis and treatment, and new research continues
to refine the understanding of these complex conditions.
 08
Lysosomal Storage Diseases:
Gaucher's Disease and Niemann-Pick
Disease
Lysosomal Storage Diseases
Overview
Definition: Genetic disorders caused by enzyme
deficiencies in lysosomes, leading to substrate
accumulation.
Impact: Affects multiple organ systems and has diverse
clinical manifestations.
Gaucher's Disease
Definition: Caused by a deficiency of the enzyme
glucocerebrosidase.

Types:
Type:1 (Non-Neuropathic): Hepatosplenomegaly, bone pain,
anemia.
Type 2 (Acute Neuropathic): Severe neurological symptoms, early
death.
Type 3 (Chronic Neuropathic): Progressive neurological symptoms.

Diagnosis: Enzyme assay, genetic testing for GBA gene

mutations.
Treatment: Enzyme Replacement Therapy (ERT), Substrate
Reduction Therapy (SRT), supportive care.
Gaucher's Disease
Niemann-Pick Disease
Definition: A group of disorders with sphingomyelin accumulation due
to enzyme deficiencies (Types A and B) or impaired cholesterol transport
(Type C).

Types:
Type A Severe neurodegeneration, hepatosplenomegaly, early death
Type B Hepatosplenomegaly, less severe neurodegeneration, longer
lifespan.
Type C Progressive neurological symptoms, cognitive decline.

Diagnosis: Enzyme assays, genetic testing for SMPD1 (Types A and B)

or NPC1/NPC2 (Type C), imaging studies.

Treatment: Type A/B: Supportive care.

Type C: Miglustat, supportive care.
Summary
● Gaucher's and Niemann-Pick diseases are serious lysosomal storage
disorders with distinct pathophysiology's and clinical outcomes.
Diagnosis involves enzyme assays and genetic testing, while
treatment varies from enzyme replacement to supportive care