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ABNORMALITIES of the
      WHITE BLOOD
CELLS


    Jose R. Villarino, RMT
Possible answers:
   A. NEUTROPHILS          J. ASTHMA
   B. LYMPHOCYTES          K. AUER ROD
   C. PATHOLOGIC           L. PELGER HUET
   D. PHYSIOOGIC           M. TOXIC
   E. 20-40 %               GRANULES
   F. 5000-10000/cumm      N. LEUCOPENIA
   G. 0-3 %                O. PARASITISM
   H. MALARIA              P. SCARLET FEVER
   I. AZUROPHILIC          Q. DOHLE BODIES
    GRANULES                R. BASKET CELLS
WBC Normal values:
   WBC Count = 5,000 – 10,000/cu mm or
                  5 – 10 x 109/L
   Differential Count:
   Neutrophil = 50 – 70 %
    Segmenter = 50 – 65 % ; Stab = 0 – 5 %
   Eosinophil = 0 – 3 %
   Basophil = 0 – 1 %
   Lymphocytes = 20 – 40 %
   Monocytes = 2 – 6 %
Quantitative abnormalities
  Leucocytosis – substantial increase in
   the WBC count.
 - Physiologic increase (no trauma/injury)
 - Pathologic increase (trauma/pathology)
 Leucopenia – substantial decrease in

   the WBC count.
 N.V. = 5,000 – 10,000/cu mm
Differential Count
Neutrophil      50 – 75 %
 segmenter      50 – 65 %
 stab            0–5%
Eosinophil      0–3%
Basophil        0–1%
Lymphocyte      20 – 40 %
Monocyte        2–6%
The 5 WBC types
Neutrophilia
       (> 7 – 8 x109/L)
   Infections, Inflammation, Metabolic
    disorders
   Acute hemorrhage, corticosteroids
   Stress, post-surgery, burns, HDN
   Lithium drugs, neoplasms
Neutropenia
    (<1.75 – 1.8109/L)
  Decreased production
 - Inherited/acquired stem cell disorder
 - Benzene toxicity, cytotoxic drugs
 Increased destruction

 - Immune mechanism, sequestration
 BM depression, IM, varicella, Typhoid

 SLE, hepatitis or any viral infections
Eosinophilia
       (> 0.7 x 109/L)
   Allergic disorders (asthma)
   Parasitic infections (nematodes)
   Skin disease (eczema)
   Hodgkin’s disease
   Scarlet Fever
   Pernicious anemia
Eosinopenia
       (< 0.05 x 109/L)
   Stress due to trauma or shock
   Mental distress
   Cushing’s syndrome
   ACTH administration
Basophil (0.3 x 109/L)
BASOPHILIA   Chronic myelocyic leukemia
             Polycythemia vera
             Hodgkin’s disease

BASOPENIA    Hyperthyroidism
             Pregnancy
Lymphocytosis
      (>4.0 x 109/L)
   Viral infections ( German measles )
   Infectious Mononucleosis (kissing dis.)
   Mumps (parotitis), pertussis
   Tuberculosis, syphilis, thyrotoxicosis
Lymphopenia
   Congestive heart failure, SLE
   Renal failure
   Advanced Tuberculosis
   High levels of adrenal corticosteroids
Monocytosis
       (>0.9 x 109/L)
   SBE, Syphilis, Tuberculosis
   Protozoan infections
   Mycotic or fungal infections
   Malaria, Systemic lupus erythematosus
   Rheumatoid arthritis
Monocytopenia
   Lymphocytic leukemia
   Aplastic anemia
QUALITATIVE CHANGES-
WBC
   Morphologic abnormalities involving
    either the nucleus or cytoplasm
   Functional abnormalities

   Inherited or Acquired
   Examination of peripheral blood or a
    bone marrow evaluation
The White blood cells:
  Nucleus details:
 - Mononuclear or Polymorphonuclear
 Granules present:

 - Granulocytic or Agranulocytic
 Function:

 - Phagocytic or Immunocytic
Abnormal granulocyte
      morphology (acquired)
   Toxic granulation, cytoplasmic vacuole
   Dohle bodies (Amato bodies)
   Azurophilic granules
   Hypersegmentation
Pathological Leucocytes
Abnormal granulocyte
       morphology (inherited)
   Alder-Reilly anomaly - dense
    azurophilic granules,
    mucopolysaccharoidoses
   May-Hegglin anomaly - Giant platelets,
    Dohle-bodies like inclusions seen even
    in monocytes
   Pelger Huet anomaly – failure of normal
    segmentation of nucleus, bi-lobed
    nucleus or stab forms only,
    “pince-nez nucleus”
Alder Reilly anomaly
May-Hegglin anomaly
Pelger Huet anomaly
Continuation:
   Chediak Steinbrinck Higashi syndrome –
    large lysosomes containing hydrolases and
    other enzymes. There is
    anemia,thrombocytopenia, leucopenia and
    increased susceptibility to infection. There is
    partial albinism & photophobia.
   Also seen in Aleutian mink, mice, cat, cattle &
    killer whale as caused by abnormal WBCs.
Chediak Higashi syndrome
Other abnormalities:
   Smudge or basket cells – squash-
    degenerated nucleus of WBCs
   Jordan’s anomaly – fat-containing
    vacuoles in WBC cytoplasm, Ichthyosis
   Twinning deformity
   Auer rod – rod-like structure seen in the
    cytoplasm of myeloblasts, diagnostic for
    Acute myeloblastic leukemia (AML)
Variants of the Lymphocytes
   Plasmacytoid lymphocyte or Turk’s
    irritation cell
   Downey cell (atypical lymphocyte)
   Transformed lymphocyte (reticular or
    pyroninophilic cell)
   Reider cell – “clover-leaf like nucleus”
   Plasma cells
Reactive lymphocytes
Downey cell
   Hallmark cell seen in cases of
    Infectious mononucleosis (kissing
    disease)
   Atypical lymphocyte (stress
    lymphocyte)
   “ballerina skirt cell”
Infectious Mononucleosis
Plasma cells
   Ovoid or fibrillary shaped
   Eccentric location of nucleus
   Perinuclear halo
   “cart-wheel pattern or spoke of the
    wheel pattern of nucleus”
    basophilic cytoplasm
Comparative morphology of plasma
cells, lymphocytes and NRBC
Inherited abnormalities involving
Monocyte-macrophage group
  MUCOPOLYSACCHAROIDOSES
 - Hunter syndrome, Hurler’s disease
 LIPIDOSES – lipid accumulation

 - Gaucher’s disease – accumulation of
   glucocerebroside due to lack of beta-
   glucosidase enzyme
 - Neimann Pick disease – sphingomyelin
   and cholesterol accumulation due to
   lack of the enzyme sphingomyelinase
Monocyte-macrophage
abnormality
WBC functions
   Neutrophil – phagocytic
   Eosinophil – phagocytic and damage to
    larval stages of parasite.
   Basophil – storage of histamine,
    involved in immediate hypersensitivity
    reaction.
   Monocyte – phagocytic, cellular and
    humoral immunity
Functions….
   Lymphocytes – immune leucocytes
   a)humoral b) lymphokines c) cytotoxic

- Not obligate end cells
- Heterogenous group of cells
- Destined to migrate
PHAGOCYTOSIS process
   Motility – random movement and
    directed movement
   Recognition
   Ingestion
   Degranulation or release of granules
   Microbial killing
Inherited functional
         abnormalities
   Job’s syndrome – defective directed
    movement, characteristic “cold boils”
   Lazy leucocyte syndrome – both
    random & directed movements are
    defective
   Chediak Higashi syndrome – failure to
    release the granules
Non-neoplastic (non-clonal)
disorders of the WBC
   Include a) growth regulation
    abnormalities, b) leukemoid reaction
    (an increased proliferative response to
    various stimuli) including bone marrow
    aplasia and hypoplasia and
    c) qualitative leucocyte disorders (both
    acquired & inherited) characterized by
    deficiency of leucocyte function.
Non-clonal disorders of WBC
Function disorders
 Defective chemotaxis, phagocytosis,
 defective killing, CGD, myeloperoxidase
 deficiency
Quantitative disorders
 Neutropenia, agranulocytosis,
 Leukemoid reaction, Infectious mono
Clonal (neoplastic) disorders
of WBC
   Derived from a single precursor cell with
    all the affected cells (progeny) showing
    features of deviation from the precursor
    cell.
   Myeloproliferative disorders
   Lymphoproliferative disorders
   Immunoproliferative disorders
Leukemoid reaction
  High WBC count = <50000/cu mm
 Toxic granulation & Dohle bodies

 Predominant band forms

 LAP score = >100

 Negative for Philadelphia chromosome

 - Translocation of genetic material from
   long arm of Chromosome 22 to Ch 9
Hodgkin’s disease
   Belongs to a group of malignant
    disorders referred as Lymphomas
   Lymphomas involved abnormal lymph
    node enlargement with replacement or
    alteration in its histologic characteristic
   The neoplastic cell involved is known as
    the Reed-Sternberg cell. Mostly
    appears as binucleated with the 2
    halves of the cell appearing as mirror
    images.
Hematopoietic malignancy
   Defined as growth or proliferation of
    one or more clones of abnormal cells.
    These cells don’t respond to normal
    control and even produce substances
    inhibiting growth of normal cells.
   These malignancy may be manifested
    in the peripheral blood as in cases of
    anemia and thrombocytopenia.
Leukemias
   In the case of WBC, these malignant cells
    may or may not circulate in the peripheral
    blood. Hence, WBC count may be increased
    or otherwise.
   Should these abnormal cells be present both
    in the bone marrow and the peripheral blood,
    the term leukemia is used.
   Aleukemic leukemia – if only confined to the
    marrow and do not circulate.
Classification of the leukemias
 According to the stem cell line involved
- Myeloid – involves the granulocytes,
  monocytes, RBCs and
  megakaryocytes. Also known as
  myeloproliferative disorders or
  nonlymphocytic leukemias.
- Lymphoid – involving the B or T cells
  and may be a leukemia or lymphoma
Classification of leukemias
  According to duration (life span)
- Acute – days to weeks (3 months)
 - greater than 30 % blasts forms
- Chronic – more than a year (1-2 years)
 - less than 10 % blast forms
Examples :
Acute myeloid leukemia   myeloblast

Chronic myelogenous      Myelocyte, metamyelocyte &
leukemia                 neutro
Acute lymphoblastic      lymphoblasts
leukemia
Chronic lymphocytic      Small mature lymph
leukemia
Erythroleukemia          > 50% of the nucleated cells
Di Guglielmo syndrome    are erythroblasts
Comments on the leukemias:
   AML – most common form of acute
    leukemias in first few months of life, in
    middle aged group and later years
   CML – more common in young & elders
   ALL – seen among children 2 – 10 y.o.
   CLL – common among > 60 years old

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Abnormalities of WBC

  • 1. ABNORMALITIES of the WHITE BLOOD CELLS Jose R. Villarino, RMT
  • 2. Possible answers:  A. NEUTROPHILS  J. ASTHMA  B. LYMPHOCYTES  K. AUER ROD  C. PATHOLOGIC  L. PELGER HUET  D. PHYSIOOGIC  M. TOXIC  E. 20-40 % GRANULES  F. 5000-10000/cumm  N. LEUCOPENIA  G. 0-3 %  O. PARASITISM  H. MALARIA  P. SCARLET FEVER  I. AZUROPHILIC  Q. DOHLE BODIES GRANULES  R. BASKET CELLS
  • 3. WBC Normal values:  WBC Count = 5,000 – 10,000/cu mm or 5 – 10 x 109/L  Differential Count:  Neutrophil = 50 – 70 % Segmenter = 50 – 65 % ; Stab = 0 – 5 %  Eosinophil = 0 – 3 %  Basophil = 0 – 1 %  Lymphocytes = 20 – 40 %  Monocytes = 2 – 6 %
  • 4. Quantitative abnormalities  Leucocytosis – substantial increase in the WBC count. - Physiologic increase (no trauma/injury) - Pathologic increase (trauma/pathology)  Leucopenia – substantial decrease in the WBC count.  N.V. = 5,000 – 10,000/cu mm
  • 5. Differential Count Neutrophil 50 – 75 % segmenter 50 – 65 % stab 0–5% Eosinophil 0–3% Basophil 0–1% Lymphocyte 20 – 40 % Monocyte 2–6%
  • 6. The 5 WBC types
  • 7. Neutrophilia (> 7 – 8 x109/L)  Infections, Inflammation, Metabolic disorders  Acute hemorrhage, corticosteroids  Stress, post-surgery, burns, HDN  Lithium drugs, neoplasms
  • 8. Neutropenia (<1.75 – 1.8109/L)  Decreased production - Inherited/acquired stem cell disorder - Benzene toxicity, cytotoxic drugs  Increased destruction - Immune mechanism, sequestration  BM depression, IM, varicella, Typhoid  SLE, hepatitis or any viral infections
  • 9. Eosinophilia (> 0.7 x 109/L)  Allergic disorders (asthma)  Parasitic infections (nematodes)  Skin disease (eczema)  Hodgkin’s disease  Scarlet Fever  Pernicious anemia
  • 10. Eosinopenia (< 0.05 x 109/L)  Stress due to trauma or shock  Mental distress  Cushing’s syndrome  ACTH administration
  • 11. Basophil (0.3 x 109/L) BASOPHILIA Chronic myelocyic leukemia Polycythemia vera Hodgkin’s disease BASOPENIA Hyperthyroidism Pregnancy
  • 12. Lymphocytosis (>4.0 x 109/L)  Viral infections ( German measles )  Infectious Mononucleosis (kissing dis.)  Mumps (parotitis), pertussis  Tuberculosis, syphilis, thyrotoxicosis
  • 13. Lymphopenia  Congestive heart failure, SLE  Renal failure  Advanced Tuberculosis  High levels of adrenal corticosteroids
  • 14. Monocytosis (>0.9 x 109/L)  SBE, Syphilis, Tuberculosis  Protozoan infections  Mycotic or fungal infections  Malaria, Systemic lupus erythematosus  Rheumatoid arthritis
  • 15. Monocytopenia  Lymphocytic leukemia  Aplastic anemia
  • 16. QUALITATIVE CHANGES- WBC  Morphologic abnormalities involving either the nucleus or cytoplasm  Functional abnormalities  Inherited or Acquired  Examination of peripheral blood or a bone marrow evaluation
  • 17. The White blood cells:  Nucleus details: - Mononuclear or Polymorphonuclear  Granules present: - Granulocytic or Agranulocytic  Function: - Phagocytic or Immunocytic
  • 18. Abnormal granulocyte morphology (acquired)  Toxic granulation, cytoplasmic vacuole  Dohle bodies (Amato bodies)  Azurophilic granules  Hypersegmentation
  • 20. Abnormal granulocyte morphology (inherited)  Alder-Reilly anomaly - dense azurophilic granules, mucopolysaccharoidoses  May-Hegglin anomaly - Giant platelets, Dohle-bodies like inclusions seen even in monocytes  Pelger Huet anomaly – failure of normal segmentation of nucleus, bi-lobed nucleus or stab forms only, “pince-nez nucleus”
  • 24. Continuation:  Chediak Steinbrinck Higashi syndrome – large lysosomes containing hydrolases and other enzymes. There is anemia,thrombocytopenia, leucopenia and increased susceptibility to infection. There is partial albinism & photophobia.  Also seen in Aleutian mink, mice, cat, cattle & killer whale as caused by abnormal WBCs.
  • 26. Other abnormalities:  Smudge or basket cells – squash- degenerated nucleus of WBCs  Jordan’s anomaly – fat-containing vacuoles in WBC cytoplasm, Ichthyosis  Twinning deformity  Auer rod – rod-like structure seen in the cytoplasm of myeloblasts, diagnostic for Acute myeloblastic leukemia (AML)
  • 27. Variants of the Lymphocytes  Plasmacytoid lymphocyte or Turk’s irritation cell  Downey cell (atypical lymphocyte)  Transformed lymphocyte (reticular or pyroninophilic cell)  Reider cell – “clover-leaf like nucleus”  Plasma cells
  • 29. Downey cell  Hallmark cell seen in cases of Infectious mononucleosis (kissing disease)  Atypical lymphocyte (stress lymphocyte)  “ballerina skirt cell”
  • 31. Plasma cells  Ovoid or fibrillary shaped  Eccentric location of nucleus  Perinuclear halo  “cart-wheel pattern or spoke of the wheel pattern of nucleus”  basophilic cytoplasm
  • 32. Comparative morphology of plasma cells, lymphocytes and NRBC
  • 33. Inherited abnormalities involving Monocyte-macrophage group  MUCOPOLYSACCHAROIDOSES - Hunter syndrome, Hurler’s disease  LIPIDOSES – lipid accumulation - Gaucher’s disease – accumulation of glucocerebroside due to lack of beta- glucosidase enzyme - Neimann Pick disease – sphingomyelin and cholesterol accumulation due to lack of the enzyme sphingomyelinase
  • 35. WBC functions  Neutrophil – phagocytic  Eosinophil – phagocytic and damage to larval stages of parasite.  Basophil – storage of histamine, involved in immediate hypersensitivity reaction.  Monocyte – phagocytic, cellular and humoral immunity
  • 36. Functions….  Lymphocytes – immune leucocytes  a)humoral b) lymphokines c) cytotoxic - Not obligate end cells - Heterogenous group of cells - Destined to migrate
  • 37. PHAGOCYTOSIS process  Motility – random movement and directed movement  Recognition  Ingestion  Degranulation or release of granules  Microbial killing
  • 38. Inherited functional abnormalities  Job’s syndrome – defective directed movement, characteristic “cold boils”  Lazy leucocyte syndrome – both random & directed movements are defective  Chediak Higashi syndrome – failure to release the granules
  • 39. Non-neoplastic (non-clonal) disorders of the WBC  Include a) growth regulation abnormalities, b) leukemoid reaction (an increased proliferative response to various stimuli) including bone marrow aplasia and hypoplasia and c) qualitative leucocyte disorders (both acquired & inherited) characterized by deficiency of leucocyte function.
  • 40. Non-clonal disorders of WBC Function disorders Defective chemotaxis, phagocytosis, defective killing, CGD, myeloperoxidase deficiency Quantitative disorders Neutropenia, agranulocytosis, Leukemoid reaction, Infectious mono
  • 41. Clonal (neoplastic) disorders of WBC  Derived from a single precursor cell with all the affected cells (progeny) showing features of deviation from the precursor cell.  Myeloproliferative disorders  Lymphoproliferative disorders  Immunoproliferative disorders
  • 42. Leukemoid reaction  High WBC count = <50000/cu mm  Toxic granulation & Dohle bodies  Predominant band forms  LAP score = >100  Negative for Philadelphia chromosome - Translocation of genetic material from long arm of Chromosome 22 to Ch 9
  • 43. Hodgkin’s disease  Belongs to a group of malignant disorders referred as Lymphomas  Lymphomas involved abnormal lymph node enlargement with replacement or alteration in its histologic characteristic  The neoplastic cell involved is known as the Reed-Sternberg cell. Mostly appears as binucleated with the 2 halves of the cell appearing as mirror images.
  • 44. Hematopoietic malignancy  Defined as growth or proliferation of one or more clones of abnormal cells. These cells don’t respond to normal control and even produce substances inhibiting growth of normal cells.  These malignancy may be manifested in the peripheral blood as in cases of anemia and thrombocytopenia.
  • 45. Leukemias  In the case of WBC, these malignant cells may or may not circulate in the peripheral blood. Hence, WBC count may be increased or otherwise.  Should these abnormal cells be present both in the bone marrow and the peripheral blood, the term leukemia is used.  Aleukemic leukemia – if only confined to the marrow and do not circulate.
  • 46. Classification of the leukemias  According to the stem cell line involved - Myeloid – involves the granulocytes, monocytes, RBCs and megakaryocytes. Also known as myeloproliferative disorders or nonlymphocytic leukemias. - Lymphoid – involving the B or T cells and may be a leukemia or lymphoma
  • 47. Classification of leukemias  According to duration (life span) - Acute – days to weeks (3 months) - greater than 30 % blasts forms - Chronic – more than a year (1-2 years) - less than 10 % blast forms
  • 48. Examples : Acute myeloid leukemia myeloblast Chronic myelogenous Myelocyte, metamyelocyte & leukemia neutro Acute lymphoblastic lymphoblasts leukemia Chronic lymphocytic Small mature lymph leukemia Erythroleukemia > 50% of the nucleated cells Di Guglielmo syndrome are erythroblasts
  • 49. Comments on the leukemias:  AML – most common form of acute leukemias in first few months of life, in middle aged group and later years  CML – more common in young & elders  ALL – seen among children 2 – 10 y.o.  CLL – common among > 60 years old