CASE HISTORY • Part 1
A 54-year-old woman with poorly controlled hypertension while on a beta-blocker is started on hydrochlorothiazide. A month later she returns for a blood pressure check and describes several days of a sore throat, fever, and chills. On examination she has a temperature of 39.5°C, a pharyngeal exudate, and submaxillary lymphadenopathy. A complete blood count (CBC) with differential is ordered STAT.
CBC: Hematocrit/hemoglobin - 40%/13 g/dL
WBC - 4.1 × 103/uL
Differential - Neutrophils 10% Monocytes 15% Lymphocytes 75%
Platelet count - 150 × 103/uL SMEAR MORPHOLOGY
Normocytic, normochromic red cells without aniso- or poikilocytosis. White cells are sparse, comprised mostly of normal-appearing lymphocytes, with a few normal-appearing neutrophils; no early neutrophil precursors (bands, myelocytes, or blasts) are seen. Platelets are normal. Questions
Given the CBC findings, what are the absolute numbers for each of the white cell lines and what abnormality is present?
What further workup is needed—both history and laboratory testing?
Quantitative disorders of neutrophils are frequently encountered in clinical practice but seldom present a diagnostic problem. For example, granulocytosis, which is an acute increase in the number of mature and immature granulocytes in circulation, is an anticipated part of the normal response to any infection. Eosinophilia and monocytosis are seen in association with allergic and inflammatory conditions. On the other hand, granulocytopenia can occur as a side effect of drug administration or as a component of the pancytopenia seen with severe marrow damage. It is an anticipated complication of cancer chemotherapy.
Qualitative disorders of neutrophil function are much less common. Again, they can occur as a complication of drug therapy. Those that result from genetic defects in granulocyte adhesion, migration, or lysozyme function are a greater diagnostic challenge.
NORMAL RESPONSE OF NEUTROPHILS TO INFECTION
The kinetics of normal neutrophil production and destruction are described in Chapter 16. In response to infection or presentation of a foreign antigen, several cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1, granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], monocyte colony-stimulating factor [M-CSF], and IL-3) are released that affect the kinetics of neutrophil production and the distribution of cells within the circulation and tissues. A single mediator of inflammation cannot be identified; however, the broad effects of TNF-α illustrate how the reaction is coordinated. Administration of TNF-α essentially duplicates all of the signs and symptoms of sepsis, including fever, hypotension, and acute respiratory distress syndrome/pulmonary edema. It is associated with concomitant changes in other cytokines that mediate the reaction to infection, such as IL-1, which stimulates the immune system, and the colony-stimulating factors (CSFs), which stimulate granulocyte production and function. Interestingly, experimental blockade of TNF-α can ablate most of the inflammatory effects of sepsis and, in some models, can prevent death from septic shock.
The earliest response to an infection is the emigration of granulocytes out of circulation and ...