Neutrophilia and Neutropenia
NEUTROPHILS
• Neutrophils are the most numerous leukocyte in the peripheral blood.
• Count: 40-70% or 2.0 – 7.0 x 10^3/μl.
• Size 13 μm
• They are easily identified on Romanowsky stain.
• Morphology shows dark purple, condensed segmented nucleus (2-5 lobes) and numerous fine pink color granules.
• More than five lobes is considered as a hypersegmented neutrophil.
• It contains many secondary and tertiary granules and secretory vesicles.
IMPORTANCE OF GRANULES CONTENTS
• Neutrophilic granules chemically composed protein, lipids, and carbohydrates.
• Cytochemical stains based on the biochemical composition of granules.
• Cytochemical stain for lipids, Sudan black B, is used to differentiate myeloid precursors from lymphoid precursors.
• Cytochemical stain for glycogen, periodic acid-Schiff (PAS) stain is used to detect glycogen in cells.
• CD markers on the neutrophil include CD13, CD15, CD16, CD11b/CD18, and CD33
X CHROMOSOME INACTIVATION
• In normal females with two X chromosomes or males with XXY chromosomes (Klinefelter syndrome), one X chromosome is randomly inactivated in each somatic cell of the embryo.
• Remains inactive in all daughter cells produced from that cell.
• The inactive X chromosome appears as an appendage of the neutrophil nucleus and is called a drumstick or Barr body or X chromatin body
NEUTROPHILIA
• Increase in the number of circulating neutrophils greater than 7.0×10^9/L is termed as neutrophilia.
• Neutrophilia may be immediate, acute and chronic.
• Immediate Neutrophilia can occur without pathologic stimulus and is probably a simple redistribution of the marginating pool to the circulating pool and it is a transit (20-30 minutes).
• It is independent bone marrow out put or tissue egress. It is also called demarginating or pseudo neutrophilia.
• Acute neutrophilia occurs usually within hours after an appropriate stimulation. Acute neutrophilia occurs when neutrophils egress from the bone marrow storage pool into the peripheral blood
• Circulating pool of neutrophils can increase by as much as 10-fold.
• Chronic neutrophilia generally follows acute neutrophilia and occurs if the stimulus for neutrophils continues beyond a few days.
• lasts from several weeks to many months.
• This results in a depleted storage pool and increased production of the mitotic pool in an attempt to meet the demand for neutrophils
• An increase in the concentration of immature forms of leukocytes in the circulation is termed a shift to the left or left shift.
MECHANISM OF NEUTROPHILIA
• Increased production
• Increased release of neutrophils from the marrow
• Shifting of marginating pool to circulating pool
• Reduced egress of neutrophils from the blood to tissues
• Combination of these mechanisms
CAUSES OF NEUTROPHILIA
A: Physiological Neutrophilia
Strenuous exercise
Stress
Temperature extremes
Pregnancy
Childbirth
Newborns
B: Pathological Neutrophilia
a. Non Malignant Neutrophilia
1. Bacterial Infection and fungal infections
Septicemia/Sepsis
Pyogenic bacteria infection
2. Inflammation and tissue damage
Myositis
Vasculitis
Cardiac infarct
Autoimmune disorders
Tissue damage from burn,
Trauma and Surgery
3. Metabolic disorder
Uraemia
Acidosis
Gout
4. Drugs and chemicals
Corticosteroids
Epinephrine
Histamine
Ethylene
Lithium carbonate
5. Acute hemorrhage or hemolysis
6. Treatment with myeloid growth factors (G-CSF)
B. Malignant Neutrophilia
1. Myeloproliferative disease
Chronic myeloid leukemia
Polycythemia vera
Myelofibrosis
Essential thrombocythemia
2. Neoplasm
Carcinoma
Lymphoma
Melanoma
NEUTROPENIA
It is the Reduction in the absolute neutrophil count (below 2.0X10^9/L) is termed as neutropenia.
• Recurrent and persistent bacterial infections are the hallmark of neutropenia
• Neutropenia may be mild (1.0-1.5X10^9/L), moderate (0.5-1.0X10^9/L) or severe (below 0.2×10^9/L).
MECHANISM OF NEUTROPENIA
• Decreased production of neutrophils
• Increased destruction, removal or utilization of neutrophils
• Abnormal distribution (Pseudoneutropenia)
• Combination of these mechanisms
CAUSES OF NEUTROPENIA
1. Decreased production of neutrophils
• A large number of conditions may lead to inadequate production of neutrophils. These may be grossly divided into two groups i.e. inherited and acquired
Inherited:
• Reticular dysgenesis (Severe combined
immunodeficiency)
• Cyclic neutropenia
• Kostmann syndrome
• Chronic idiopathic neutropenia
Acquired:
• Aplastic anemia
• Bone marrow infiltration
Leukemia
Lymphoma
Tumors
Tuberculosis
• Vitamin B12 or folate deficiency
• Myelodysplastic syndrome
Infections:
• Bacterial: Typhoid, bacillary dysentery, tuberculosis;
• Viral: Influenza, measles, dengue, infectious mononucleosis, rubella, infectious hepatitis
• Protozoal: Malaria, kala-azar etc.
• Drug induced: Cytotoxic chemotherapy, radiation, chloramphenicol, penicillins, cephalosporins, phenothiazine, phenylbutazone, gold, antithyroid, quinidine, anticonvulsants, alcohol
2. Increased destruction
• Neutropenia may also occur when the peripheral depletion rate exceeds the bone marrow production rate for neutrophils.
Associated conditions
• Hypersplenism
• Immune mediated
• Drug induced
• Associated with collagen vascular disease (Felty syndrome, systemic lupus erythematosus)
• Complement mediated (hemodialysis, cardiopulmonary bypass)
3. Abnormal Distribution
• Abnormal transfer of neutrophils from circulating pool to marginating pool leads to neutropenia known as shift neutropenia or pseudo-neutropenia. This may be observed in:
• Idiopathic hemolytic anemia
• Cirrhosis of liver
• Macroglobulinemia
• Drugs
• Stress
