CMS 201

WBCs and lymphoid disorders:

Overview – Part 1

Ahmed Abdallah Abdalkader, MD

Lecturer of Internal Medicine, ASU, GU.
F A C U L T Y O F M E D I C I N E

F A L L 2 0 2 2 / 2 0 2 3
 Assignment 4

1) What are the treatment lines of ITP?

2) What are the treatment lines of Hemophilia?
3) What are the common drugs that affect the thrombosis and
coagulation pathways and how?
 By the end of this lecture, you should be able to:
1. Know the normal differential WBCs count.
2. Know causes of abnormal WBC count.
3. differentiate the unusual benign leucocyte disorders.
4. Understand the pathophysiology of leucocyte disorders.
5. Know the clinical anatomy and physiology of lymphatic system.
6. Classify the causes lymphadenopathy.
7. Classify the causes of splenomegaly.
8. Classification of different WBCs and lymphoid disorders
Hematopoiesis
 Mature
Myeloid Cells
 Assessment of Circulating WBC

• The total white blood cell count (WBC) and differential

are measured in an automated counter.
• WBC reflects the circulating pool of myeloid and
lymphoid cells.
• WBC in each microliter (ml;mm3) is reported.
• Relative proportion of each type of WBC is indicated by a
percentage.
• Absolute number is the percentage of each type of WBC
multiplied by the total WBC.
White Blood Cell Counts: Normal Ranges
Neutrophil Maturation
Neutrophil Maturation - Proliferative Phase
Neutrophil - Maturation Phase
Fate of the mature neutrophil
 Neutrophil disorders

➢ Disorders of neutrophil number

➢ Disorders of neutrophil Function
Disorders of
Neutrophil
Number
 Neutrophilia
➢Acute shift from marginating ➢Chronic Stimulation
to circulating pool • Excess cytokine stimulates proliferative
pool, ↑ total WBC
• ↑ measured WBC, not total WBC

✓Causes: ✓Causes:
• Steroid treatment • Bacterial Infection
• Exercise • Fungal infection
• Epinephrine • Down's Syndrome
• Hypoxia • Pregnancy/Eclampsia
• Seizures • Chemotherapy recovery
• Other stress factors • Myeloproliferative disorders
• Marrow metastases
 Neutropenia
Decreased Increased Shift to
Production Destruction Marginating Pool
Bone marrow Peripheral Move from the
circulation circulating pool to
attach along the
vessel wall
Medication: Autoimmune Severe infection
Chemotherapy diseases Endotoxin release
Antibiotics, Vit.B12 (Rheumatoid Hemodialysis
or Folate arthritis, SLE, etc.) Cardiopulmonary
deficiency, bypass
Malignancy, etc.
 Role of Neutrophil in acute inflammation
• Responds to chemotactic factors released from damaged tissue
• Rolls and attaches to the endothelial cell wall
– protein and carbohydrate interactions (selectins, integrins and their ligands).
• Becomes activated by chemotactic factors
• Tightly adheres through the integrin family of proteins.
• Migrates across the endothelial cell wall.
• Phagocytizes organisms so that they are contained within a vesicle or
phagosome.
• Releases granule products and reduced oxygen species (e.g., hydrogen
peroxide and superoxide) to kill organisms
Role of Neutrophil in acute inflammation
Respiratory burst
Respiratory burst
 Disruption of Neutrophil Function

1. Defects in leukocyte structure

• Example: membrane fusion defect in Chédiak-Higashi syndrome
2. Defects in leukocyte function
a. Leukocyte adhesion defect (LAD)
• Examples: deficient selectin or CD11a/CD18 adhesion
b. Phagocytosis defect
• Example: decreased immunoglobulins in Bruton agammaglobulinemia
c. Microbicidal defect
• Example: deficiency myeloperoxidase (MPO) or NADPH oxidase
 Eosinophilia

• Conditions:
– Neoplasm (Hodgkin’s disease, lymphoma other tumors)
– Allergies: drugs, environmental
– Asthma
– Collagen vascular diseases-vasculitis
– Parasitic infection
• Idiopathic hyper-eosinophilia: elevated eosinophil count
associated with organ dysfunction (GI, skin, CNS, cardiovascular).
– Levels > 5000/µl requires treatment with steroids,
immunosuppressives and antihistamines.
 • Conditions:
– Allergies
– Infection
– Endocrinopathies
Basophilia
– Myeloproliferative disorders
– Systemic mastocytosis
• Symptoms due to excess
histamine release
 Monocyte-Macrophages

▪ Monocytes: circulating precursor of the tissue

macrophage.
▪ Also known as the reticuloendothelial system
▪ Average count 300 cells /ml
▪ Range 0-800 cells/ml
 • Conditions:
–Malignancy
–Granulomatous disease
Monocytosis –Autoimmune diseases
–Infections
• Malaria, TB
• Rocky Mountain Spotted fever
• Leishmaniasis, Brucellosis
 • Conditions:
Decreased –Steroids
eosinophils,
–Hypercortisolism
basophils &
monocytes –Chemotherapy
–Bone marrow suppression
Mature lymphoid Cells
Disorders of
Lymphocyte
Numbers
 Lymphocytosis
(1)Viral infections.
✓Examples: Infectious Mononucleosis caused by Epstein-Barr virus
(EBV) and cytomegalovirus (CMV) infections
(2) Bacterial infections.
✓Examples: whooping cough (Bordetella pertussis) and TB
(3) Drugs.
✓Examples: phenytoin and tetracycline
(4) Graves disease (hyperthyroidism).
(5) Neoplasia.
✓Example: chronic lymphocytic leukemia (CLL)
 Atypical (reactive) lymphocytosis
➢Definition:
A benign, reactive lymphocyte in the peripheral
blood that is produced in response to antigen
stimulation of the immune system.
✓Larger than a normal lymphocyte because it
contains more cytoplasm and has a larger nucleus
that contains prominent nucleoli
✓Cytoplasm is frequently indented by the
surrounding RBCs.
➢Causes:
✓Infection: IM, viral hepatitis, CMV infection, and
toxoplasmosis
✓Drugs (e.g., phenytoin).
 Lymphopenia
(1) HIV caused by lysis CD4T helper cells.
(2) Immunodeficiency disorders.
(a) DiGeorge syndrome (T-cell deficiency).
(b) severe combined immunodeficiency (SCID; B- and T-cell deficiency).
(c) Bruton agammaglobulinemia (B-cell deficiency).
(3) Immune destruction.
✓Examples: SLE
(4) Drugs.
✓Examples: corticosteroids, cyclophosphamide, and cytotoxic chemotherapy.
(5) Ionizing radiation.
Unusual benign leukocyte reactions

➢ Leukemoid reaction
➢ Leuko-erythroblastosis
(leuko-erythroblastic reaction)
 Leukemoid reaction
Definition
An absolute leukocyte count that is usually >25,000 to 30,000 cells/mm3.
Reaction may involve neutrophils, lymphocytes, or eosinophils.
Epidemiology
✓ Normal bone marrow response to cytokines released by cells (e.g.,
lymphocytes, macrophages) to infection (most common) or trauma.
✓ Similar to CML
❑ But Alkaline phosphatase score is increased, no Philadelphia chromosome.
✓ Examples include:
a) Neutrophilic leukocytosis associated with perforated appendicitis.
b) Lymphocytosis associated with whooping cough.
c) Eosinophilia associated with cutaneous larva migrans.
 Leukemoid reaction

Normal Leukemoid reaction

 Leuko-erythroblastosis
(leuko-erythroblastic reaction)
Definition
The presence of immature bone marrow WBCs and nucleated red blood cells
(RBCs) in the peripheral blood (“peripheralization” of the bone marrow),
irrespective of the total leukocyte count.
Epidemiology
✓ A leucoerythroblastic reaction normal bone marrow :
• severe acute hemolytic anemia (e.g., sickle cell disease).
✓ A leucoerythroblastic reaction with an abnormal bone marrow include:
a) Bone marrow infiltrative disease (e.g., amyloidosis).
b) Metastatic malignancy (e.g., breast cancer).
c) Granulomatous disease (e.g., TB, systemic fungal disease, sarcoidosis).
d) Hematologic malignancies (e.g., acute leukemia, multiple myeloma) chronic
myeloproliferative diseases (e.g., primary myelofibrosis).
 Leuko-erythroblastosis
(leuko-erythroblastic reaction)
Peripheral Blood findings include:
(1) myeloblasts, progranulocytes, and other leukocyte precursors.
(2) nucleated RBCs (NRBC) and teardrop RBCs (if fibrosis is present).

Leukoerythroblastic reaction. The

solid arrow shows a teardrop red
blood cell (RBC). Immature myeloid
cells are also present in a nucleated
RBC (interrupted arrow).
Lymphatic System
 Physiology and anatomy:
✓ Lymph vessels, ducts, and nodes.
✓ Protects body from infection by filtering
bacterial and nonbacterial products.
Lymphatic System ✓ Prevents waste products from entering
circulatory system.
✓ T cell maturation (Thymus)
✓ Site of primary immune response.
✓ Dependent on vascular system.
 Lymphoid organs are classified as:
➢ Primary lymphoid organs
Locations of ✓ Thymus
lymphoid ✓ Bone marrow
tissue ➢ Secondary (effector) lymphoid organs/tissue
✓ Spleen & lymph nodes (organs), tonsils.
✓ MALT (Peyer’s patches)
Locations of
lymphoid
tissue
Lymphadenopathy
 Lymphadenopathy
1. Epidemiology
a. Age
(1) Persons <30 years old
(a) Lymph node enlargement is usually a benign process (∼80% of
cases).
(b) In children, lymphadenopathy is the most common neck mass.
• Infection is the most common cause of the lymphadenopathy.
• Viral causes include adenovirus, rhinovirus, and enterovirus, all of
which may cause an upper respiratory infection.
• Bacterial causes include infections caused by Staphylococcus aureus
and Streptococcus pyogenes. Other significant causes include atypical
mycobacterium, Bartonella henselae (cat scratch disease), and
tuberculosis.
 Lymphadenopathy

1. Epidemiology
a. Age
(2) Persons >30 years old
(a) Lymph node enlargement is usually a malignant process
(∼60% of cases).
(b) Examples of a malignant lymph node process include
metastatic cancer (most common) or a primary lymph node
malignancy (e.g., malignant lymphoma).
 Lymphadenopathy

1. Epidemiology
b. Causes
(1) Reactive lymphadenitis.
• Hyperplasia of B cells, T cells, or histiocytes (Infections,
Autoimmune diseases, Drugs).
(2) Infiltrative disease.
• Examples of infiltrative diseases include metastasis
(most common) and malignant lymphoma.
 Lymphadenopathy
2. Clinical findings
a. Painful lymph nodes imply inflammation (e.g., infection, autoimmune disease).

(1) Localized painful lymphadenopathy

(a) Occurs when nodes drain sites of infection (e.g., tonsillitis).
(b) Most common sites are the anterior cervical nodes (e.g., tonsillitis) and
the inguinal nodes (e.g., STDs “Chancroid”).

(2) Generalized painful lymphadenopathy

(a) Primarily seen in systemic disease.
(b) Examples: infectious mononucleosis, SLE.
 Lymphadenopathy
2. Clinical findings
b. Painless lymph nodes imply a malignancy (Lymph nodes that are indurated and
fixed to surrounding tissue are likely malignant).

(1) Localized painless lymphadenopathy

(a) Occurs when lymph nodes are draining a primary cancer site (axillary
lymph nodes in breast cancer and inguinal lymph nodes in vulvar squamous
cell carcinoma (SCC).
(b) Also occurs in primary cancers involving lymph nodes (e.g., Hodgkin
lymphoma [HL] and other types of malignant lymphoma).

(2) Generalized painless lymphadenopathy

(a) Occurs in the majority of acute and chronic leukemias.
(b) Also occurs in different types of malignant lymphoma.
Splenomegaly
 Splenomegaly
1. Causes of splenomegaly:
a. “Work hypertrophy” caused by increased immune response:
• Infectious mononucleosis, subacute bacterial endocarditis, and malaria.
b. Congestion:
• Splenic vein thrombosis and PH.
c. RBC destruction work hypertrophy:
• Hereditary spherocytosis, pyruvate kinase deficiency, and β-thalassemia major.
d. Myeloproliferative disease (MPD):
• Polycythemia vera (PV), myelofibrosis (MF), and essential thrombocythemia (ET).
e. Neoplastic disease:
• Acute and chronic leukemias and malignant lymphoma.
f. Infiltrative disease:
• Primary and secondary amyloidosis, sarcoidosis, glycogen storage disease.
 Splenomegaly
2. Clinical picture:
a. Left upper quadrant (LUQ) pain.
b. Hypersplenism
1. Definition: An exaggerated state of splenic function
• RBCs, WBCs, and platelets, either singly or in combination, are sequestered and
destroyed.
2. Most common cause is PH associated with cirrhosis of the liver.
3. Clinical findings include:
a. Splenomegaly.
b. Peripheral blood cytopenias (anemia, thrombocytopenia, and neutropenia,
alone or in combination).
c. Compensatory reactive bone marrow hyperplasia (Increased reticulocytes).
d. Correction of cytopenias with splenectomy.
WBCs and lymphoid Disorders

A. Benign

1. Benign qualitative WBCs disorders.

2. Benign quantitative WBCs disorders.

3. Infectious mononucleosis.

4. Benign lymphadenopathy.

5. Benign splenomegaly.
WBCs and lymphoid Disorders

A. Malignant

1. Acute leukemias.

2. Chronic leukemias.

3. Myeloproliferative disorders

4. Plasma cell disorders.

5. Lymphomas.
 Assignment 5

1) What are the classification criteria for APL syndrome?

2) How to treat a case of DIC ?
3) How can CMV virus affect immunocompromised patient?
THANK YOU