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ABNORMALITIES of the
WHITE BLOOD
CELLS
Possible answers:
■ A. NEUTROPHILS
■ B. LYMPHOCYTES
■ C. PATHOLOGIC
■ D. PHYSIOOGIC
■ E. 20-40 %
■ F. 5000-10000/cumm
■ G. 0-3 %
■ H. MALARIA
■ I. AZUROPHILIC
GRANULES
■ J. ASTHMA
■ K. AUER ROD
■ L. PELGER HUET
■ M. TOXIC GRANULES
■ N. LEUCOPENIA
■ O. PARASITISM
■ P. SCARLET FEVER
■ Q. DOHLE BODIES
■ 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
leukemia
Myelocyte, metamyelocyte &
neutro
Acute lymphoblastic
leukemia
lymphoblasts
Chronic lymphocytic
leukemia
Small mature lymph
Erythroleukemia
Di Guglielmo syndrome
> 50% of the nucleated cells
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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WBC Abnormalities.ppt.pdf

  • 2. Possible answers: ■ A. NEUTROPHILS ■ B. LYMPHOCYTES ■ C. PATHOLOGIC ■ D. PHYSIOOGIC ■ E. 20-40 % ■ F. 5000-10000/cumm ■ G. 0-3 % ■ H. MALARIA ■ I. AZUROPHILIC GRANULES ■ J. ASTHMA ■ K. AUER ROD ■ L. PELGER HUET ■ M. TOXIC GRANULES ■ N. LEUCOPENIA ■ O. PARASITISM ■ P. SCARLET FEVER ■ Q. DOHLE BODIES ■ 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
  • 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 leukemia Myelocyte, metamyelocyte & neutro Acute lymphoblastic leukemia lymphoblasts Chronic lymphocytic leukemia Small mature lymph Erythroleukemia Di Guglielmo syndrome > 50% of the nucleated cells 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