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DIFFERENTIAL SLIDES LEGEND
CYCLE 39 SLIDE 2
BACTERIAL INFECTION
The response of bone marrow to infection is very variable, depending on the nature and chronicity of the infection, the age of the subject and the presence of any associated diseases. The response differs according to whether the infection is bacterial, rickettsial, viral or fungal. The peripheral blood and bone marrow response to infection are non specific and similar changes occur in many other conditions, including trauma and tissue damage, age , administration of growth factors, carcinoma, Hodgkin lymphoma, non Hodgkin lymphoma and other autoimmune disorders such as systemic lupus erythematosus. Only a minority of patients with an infection show peripheral or bone marrow changes suggestive of a particular microorganism.
Peripheral blood
Acute bacterial infections are the most common cause of neutrophil leucocytosis. Toxic granulation, Döhle bodies and metamyelocytes may be present in the blood. Leukemoid reactions with a white cell count >50 x109/L and granulocyte precursors in the blood may occur in severe infections, particularly in infants and young children. The neutrophil alkaline phosphatase (NAP) score is raised in contrast to the low NAP score in chronic myeloid leukaemia. Mild anemia is common if the infection is prolonged. Severe haemolytic anaemia occurs in bacterial septicaemias, particularly those caused by Gram – negative organisms, where there is usually associated DIC. DIC dominates the clinical picture with certain infections. The acute phase response to infections is accompanied by a rise in coagulation factors and a fall in natural anticoagulants.
Bacterial infections may be acute and life-threatening or chronic and relapsing. They may elicit non- inflammatory, pyogenic, granulomatous or lympho-histocytic reactions. The most common tissue response, however, in acute inflammation is dominated by neutrophils. Although studies of other indicators of infection such as sedimentation rate and C-reactive protein have been conducted, they are less helpful than the total leukocyte count (WBC) in the acute care setting of the emergency department. In addition, the volume of blood required for these tests and the delay in obtaining results make these tests impractical. The WBC is presently the most readily available marker. The relationship between acute infectious diseases and WBC, absolute neutrophil count (ANC) and increased number of band neutrophils has been recognized for many years.
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P.O. Box 131375, Bryanston, 2074
Ground Floor, Block 5 Bryanston Gate, 170 Curzon Road Bryanston, Johannesburg, South Africa
804 Flatrock, Buiten Street, Cape Town, 8001
www.thistle.co.za Tel: +27 (011) 463 3260 Fax: +27 (011) 463 3036 Fax to Email: + 27 (0) 86‐538‐4484 e‐mail : [email protected]
In adults the usual haematological response to an acute bacterial infection is neutrophil leucocytosis with a left shift (an increase of band forms and possibly the appearance of neutrophil precursors in the peripheral blood). The neutrophils usually show toxic granulation and sometimes Döhle bodies and cytoplasmic vacuolation. When there is a severe bacterial infection; in neonates, alcoholics and patients with reduced bone marrow reserves, neutrophilia does not occur but there is a left shift with the above ‘toxic” changes in neutrophils. Some bacterial infections, specifically typhoid, paratyphoid, tularaemia and brucellosis, are categorised by neutropenia rather than neutrophilia. In severe infection, particularly if there is shock or hypoxia, nucleated red blood cells may appear in the blood, the presence of both granulocyte precursors and nucleated red cells being referred to as leuco-erythroblastosis. The lymphocyte count is reduced but a few atypical lymphocytes including plasmacytoid lymphocytes and plasma cells may be present. The eosinophil count is reduced during acute infection but eosinophilia can occur during recovery.
Toxic granulation of neutrophil Diagram of a left shift Toxic changes in neutrophils
Children may respond to bacterial infection with lymphocytosis rather than neutrophilia, and certain bacterial infections, particularly whooping cough and sometimes brucellosis, are characterised by lymphocytosis. In bacterial infection the platelet count is often reduced but sometimes increased. Certain bacterial infections can be complicated by haemolytic anaemia. Infection by Escherichia coli or Shigella species can be followed by micro-angiopathic haemolytic anaemia as part of haemolytic uraemic syndrome. Sepsis due to Clostridium Welchii can be complicated by acute haemolysis with spherocytic red cells. Mycoplasma infection is commonly associated with the production of cold auto antibodies so that red cell agglutinates are present in blood films made at room temperature; haemolytic anaemia may sometimes occur.
Rarely, neutrophils contain phagocytosed bacteria. The presence of bacteria, either extracellular or within neutrophils, is usually only seen in overwhelming infections, particularly when there is associated hyposplenism. In Relapsing fever, however, the characteristic spiral organisms of Forrelia species appear regularly in the bloodstream and are seen lying free between red cells. The detection of organisms within leucocytes is facilitated by examination of buffy coat films.
In more chronic infections, there may be aneamia, increased Rouleaux formation, increased background staining and monocytosis. Anaemia is initially normocytic and normochromic but as the infection becomes increasingly chronic, the anaemia develops the characteristics of the anaemia of chronic disease with the cells produced being hypochromic and microcytic.
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P.O. Box 131375, Bryanston, 2074
Ground Floor, Block 5 Bryanston Gate, 170 Curzon Road Bryanston, Johannesburg, South Africa
804 Flatrock, Buiten Street, Cape Town, 8001
www.thistle.co.za Tel: +27 (011) 463 3260 Fax: +27 (011) 463 3036 Fax to Email: + 27 (0) 86‐538‐4484 e‐mail : [email protected]
Bone Marrow Cytology
In severe bacterial infection, the bone marrow features reflect those of the peripheral blood. There is granulocytic hyperplasia with associated toxic changes. In overwhelming infection, the marrow sometimes shows an increase of granulocyte precursors with few maturing cells. Erythropoiesis is depressed and erythroblasts show reduced siderotic granulation. When there is thrombocytosis, megakaryocytes may be increased. Macrophages are increased and, in a minority of patients with severe infection, prominent haemophagocytosis occurs. When infection is chronic an increase of iron stores is apparent. Microscopy or bone marrow culture occasionally provides evidence of a specific infection.
References 1. Bone Marrow Pathology , Edition 3 , Barbara J Bain
Questions 1. Discuss the Bone Marrow Cytology in bacterial infections. 2. Discuss the possible changes in the peripheral blood of a patient with a bacterial infection. 3. Discuss the response to a bacterial infection in children.
Thistle QA is a SANAS accredited organisation, No: PTS0001 Accredited to ISO guide 43 and ILAC G13 Certificate available on request or at www.sanas.co.za