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PA18.1-2 | Reactive Leucocytosis, Leucopenia & Lymphocytosis — Part 1
CLINICAL SCENARIO
A 24-year-old medical student presents to the college health centre with fever, sore throat, and marked fatigue for five days. Her CBC shows a WBC of 14 × 10⁹/L. The intern labels it 'leucocytosis — probably bacterial, start antibiotics.' The differential, however, shows 62% lymphocytes, many with irregular, lobulated nuclei. The senior resident stops the prescription and asks for a monospot test.
The total WBC count told one story; the differential count told another. Today you will learn to read both — and to tell reactive from malignant before a single drug is prescribed.
RECALL
Before we go further, activate what you already know:
- From Physiology (Year 1): What are the five types of white cells counted in a differential? What is the approximate normal percentage of each?
- From Biochemistry: What role do cytokines such as G-CSF and IL-6 play in haematopoiesis?
- From Anatomy: Where does granulopoiesis occur in an adult? What changes this in disease?
Jot your answers before reading on. Noticing gaps now will make the content stick better.
Normal WBC Count and the Differential
The total leucocyte count (TLC) in a healthy adult is 4.0–11.0 × 10⁹/L. Values above 11 × 10⁹/L are called leucocytosis; values below 4.0 × 10⁹/L are leucopenia.
The differential count expresses each cell type as a percentage and an absolute number. Absolute values matter more than percentages for clinical decisions.
| Cell type | Normal % | Absolute (× 10⁹/L) |
|---|---|---|
| Neutrophils | 50–70 % | 1.8–7.5 |
| Lymphocytes | 20–40 % | 1.0–4.8 |
| Monocytes | 2–8 % | 0.2–1.0 |
| Eosinophils | 1–4 % | 0.04–0.4 |
| Basophils | 0–1 % | 0–0.1 |
Relative leucocytosis — one cell type rises while others fall — can make the total count appear normal. Always assess absolute numbers.
Neutrophilia: Causes and Mechanism
Neutrophilia is defined as an absolute neutrophil count > 7.5 × 10⁹/L.
Physiological causes include physical exercise, emotional stress, pregnancy (third trimester), and the neonatal period — all mediated by demargination (cells shifting from the marginating pool to circulating pool).
Pathological causes — the common clinical scenarios:
- Bacterial infections — gram-positive and gram-negative organisms trigger G-CSF and IL-8 release, accelerating marrow output and demargination. This is the most common cause worldwide.
- Inflammatory and tissue-necrotic conditions — myocardial infarction, burns, surgery, trauma, and connective tissue diseases. The same cytokine cascade drives marrow release.
- Steroid therapy and Cushing's syndrome — corticosteroids impair neutrophil margination and apoptosis, raising the circulating count without a true increase in marrow output.
- Metabolic disorders — diabetic ketoacidosis, uraemia, eclampsia, gout.
- Drugs — lithium, colony-stimulating factors (G-CSF used in chemotherapy protocols).
- Haematological — early myeloproliferative disease (CML — discussed below), polycythaemia vera.
Remember: neutrophilia is a response, not a diagnosis. The differential count morphology is your next clue.
Left Shift, Toxic Granulation, and Döhle Bodies
In severe bacterial infection or major tissue injury, the marrow releases immature granulocytes prematurely. This produces a left shift — the appearance of band neutrophils (non-segmented forms), and in more severe cases, metamyelocytes and myelocytes in the peripheral blood.
Two additional morphological markers of neutrophil stress are diagnostically important:
- Toxic granulation: enlarged, darkly staining primary (azurophil) granules in neutrophil cytoplasm. Caused by accelerated granulopoiesis with incomplete secondary granule synthesis. Seen in severe sepsis and major burns.
- Döhle bodies: pale blue-grey, round cytoplasmic inclusions composed of rough ER remnants. Accompany toxic granulation in severe infections, burns, and pregnancy. They are not Auer rods (which are malignant).
⚑ AI image — pending faculty review (auto-QA score 4/10; best of 3 attempts)
Toxic Granulation and Döhle Body in Band Neutrophil
When left shift is accompanied by nucleated red blood cells (NRBCs) in the peripheral blood, the picture is called a leukoerythroblastic reaction — discussed separately below.