abnormalities of wbc

ABNORMALITIES of the WHITE BLOOD CELLS

Jose R. Villarino, RMT

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 leukemiaPolycythemia veraHodgkin’s disease

BASOPENIA HyperthyroidismPregnancy

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 disordersDefective 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 myelogenousleukemia

Myelocyte, metamyelocyte & neutro

Acute lymphoblasticleukemia

lymphoblasts

Chronic lymphocyticleukemia

Small mature lymph

ErythroleukemiaDi 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