MLAB 1315- Hematology Keri Brophy-Martinez

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MLAB 1315- HematologyKeri Brophy-Martinez

• Unit 18 Disorders of Neutrophils

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Neutrophil Function

• The contents of primary, secondary and tertiary
  granules in neutrophils are enzymes which are
  involved in killing and digesting bacteria and
  fungi.
• Shift to the left is the early release of
  metamyelocytes and bands from the bone marrow
  reserve into the blood stream.

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Neutrophil Function

• Primary function is phagocytosis which occurs in
  three stages.
• Migration and diapedesis
• Chemotaxis is the process of directional
  migration which occurs under the guidance of
  chemoattranctants which are produced by the site
  of injury.
• The neutrophil transforms from smooth and round
  to rough and flat.
• Diapedesis is the movement of the neutrophil
  through the vessel wall.

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Neutrophil Function

• Opsonization and recognition
• Opsonization is the mechanism which facilitates
  recognition and attachment to the organism to be
  ingested.
• After the bacteria is coated by immunoglobulin
  and complement, it is referred to as an opsonin.

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Neutrophil Function

• Phagocytosis Ingestion, killing and digestion
• The cytoplasm of the neutrophil forms a pseudopod
  which surrounds and envelops the microorganism
  forming a vacuole called a phagosome.
• Cytoplasmic granules migrate to the vacuole and
  release their lytic contents which kill and
  digest the organism.

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Response to infection - neutrophilia

• More pluripotent stem cells are committed to
  become granulocytes.
• The generation time of myelocytes is shortened.
• Myelocytes undergo an extra division.
• The transit time through the bone marrow is
  shortened.
• Leukemoid reaction is an advanced degree of
  leukocytes in the blood that is not a result of
  leukemia. The absolute neutrophil count (ANC) is
  increased. These changes occur with bacterial
  and viral infection, pregnancy, massive trauma,
  drug reactions and other toxic states.
• The cytochemical stain, Leukocyte Alkaline
  Phosphatase, is used to differentiate leukemoid
  reaction from chronic myelogenous leukemia (CML)
• Morphologic changes are the presence of toxic
  granulation, Dohle bodies and cytoplasmic
  vacuolization.

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Disorders of neutrophils

• Quantitative
• Neutropenia - ANC lt1.5 x 109/L
• Acquired
• Infection
• Most commonly caused by Staphylococcus aureus
  which is normal flora , gram-negative organisms
  from the GI tract and nosocomial infections such
  as Pseudomonas. Nosocomial infections are those
  acquired in the hospital or healthcare
  environment. They are prevented mainly by good
  handwashing between patients.
• Drug-induced
• Autoimmune
• Congenital
• Splenic sequestration

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Disorders of neutrophils

• Qualitative
• Chemotaxis disorders
• Cytoplasmic granules
• Myeloperoxidase deficiency causes abnormal
  killing of microbes
• Chediak-Higashi Syndrome
• Rare autosomal recessive condition characterized
  by partial albinism, recurrent bacterial
  infections, mild bleeding tendencies and the
  present of giant lysosomal granules in leukocytes
  and platelets.
• Usually fatal in childhood.
• Moderate neutropenia and dysfunctional phagocytic
  activity due to depressed chemotaxis and delayed
  granulation.

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Disorders of neutrophils

• Defect in microbicidal activity
• Chronic granulomatous disease
• A group of genetic disorders in which neutrophils
  and monocytes ingest, but cannot kill certain
  microorganisms because the oxidase activity is
  abnormal.
• The bacteria are not killed and the patient dies
  of infection early in life
• Diagnosis is established by the absence of a blue
  color change in the nitroblue tetrazolium test
  (NBT).

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Disorders of NeutrophilsWBC Anomalies

• These are abnormalities in the neutrophil
  morphology that do not cause disease.
• Hypersegmentation - larger than normal
  neutrophils with 6 or more nuclear lobes.
• Pelger-Huet anomaly - neutrophil nucleus is
  bi-lobed or has no lobes. May have a pince-nez
  appearance. Can be real or pseudo caused by drug
  ingestion or leukemia.
• Alders anomaly -Prominent dark-staining coarse
  cytoplasmic granules are found in neutrophils,
  eosinophils, basophils, monoctes and sometimes
  lymphocytes. Granules are precipitated
  mucopolysaccharides.
• May-Hegglin anomaly - large blue cytoplasmic
  inclusions resembling Dohle bodies are found in
  neutrophils and sometimes lymphs and monos.
  Thrombocytopenia and giant platelets are also
  seen in this anomaly