Hema 2 Lec Module 17: NONMALIGNANT REACTIVE DISORDERS OF LEUKOCYTES

non-malignant reactive disorders

These cells only function is to protect the body against invasion and undergo physical changes (that is evaluated microscopically)

Leukocytosis and Leukocytopenia

what are the 2 Quantitative physical changes in non-malignant reactive disorders?

Adult

Determine whether the Leukocyte is from an adult, child, or infant based on the reference value:

4.8 - 10.8 x 10^9/L

Children

Determine whether the Leukocyte is from an adult, child, or infant based on the reference value:

4.5 - 13.5 x 10^9 /L

Infants

Determine whether the Leukocyte is from an adult, child, or infant based on the reference value:

6 - 17.5 x 10^9 /L

10 - 11 x 10^9 /L

What is the high reference value of a leukocyte for an adult?

3-4 x 10^9 /L

What is the low reference value of a leukocyte for an adult?

LEUKOCYTOSIS

- Increase in on or more of the cell types

- Leukocyte count >11 x 109 /L

LEUKOPENIA

- Decrease in neutrophils, lymphocytes or all cell types

- Leukocyte count <3 x 109 /L

PANCYTOPENIA

Reduction in the number of RBCs, WBC, and platelets

Neutrophilia and Neutropenia

what are the 2 quantitative abnormalties in Leukocytes

PHYSIOLOGIC NEUTROPHILIA

- Response to therapy

- Physical or emotional stimuli

pseudoneutrophilia

"stimuli": the neutrophils shift or marginates cells to the circulating pool (???)

Exercise, Excessive temperature, Nausea, Vomiting, Pregnancy and labor

state the 5 physical stimuli in physiologic neutrophilia

Rage, Panic, Stress

state the 3 emotional stimuli in physiologic neutrophilia

catecholamine release

Mediated by ___________________ -> Involves norepinephrine and epinephrine which is induced by stress

False. it lasts for a FEW HOURS

True of False: In Physiologic Neutrophilia, it is transient, and lasts for a few seconds.

Infections, Drug, Inflammatory

what are the 3 kinds of pathologic neutrophilia?

Infections

Determine the kind of Pathologic Neutrophilia:

- Pyogenic bacteria (cocci and bacilli)

- Certain viruses

- Fungi (Actinomyces)

- Some Spirochetal & Rickettsial organisms

Drugs

Determine the kind of Pathologic Neutrophilia:

Lithium

- A common antidepressant

- Can cause direct stimulation of hematopoiesis

Inflammatory

Determine the kind of Pathologic Neutrophilia:

- There is a pathologic neutrophilia when it responds to tissue injury

- Neoplasms

- Metabolic disorders

- Acute hemorrhage

- Thermal injury

- Parasitic invasions

Main mechanism

_______________: release of substances by the dead or dying cells that act as a chemotactic agent or marrow-releasing agents or stimulators of marrow cell production.

Acute and Chronic

what are the 2 kinds of reactive neutrophilia?

neutrophilic left shift

Acute and Chronic reactive neutrophilia are frequently accompanied by increased numbers of immature forms called as __________________

Neutrophilic shift

- increased numbers of circulating nonsegmented/ immature neutrophils

- increased neutrophilic bands and myelocytes

Inherited and Acquired Stem Cell Disorders

what are the 2 types of decreased neutrophil production?

- Ionizing radiation

- Chemicals (benzene)

- Cytotoxic drugs

- Marrow replacement

- Nutritional deficiencies

what are the 5 stated examples of acquired stem cell disorders?

- Bacteria (typhoid, etc.)

- Viruses (measles, etc.)

what are 2 examples of infections in an increased neutrophil destruction?

Agranulocytosis

_________________ is applied when there is an extreme neutropenia. Count: <0.5 x 109/L.

- Isoimmune

- Autoimmune (HA, ITP)

- Drug-induced

what are 3 examples of immune reactions in an increased neutrophil destruction?

DECREASED NEUTROPHIL PRODUCTION

Determine whether it is under decreased neutrophil production or increased neutrophil destruction: Inherited Stem Cell Disorders

INCREASED NEUTROPHIL DESTRUCTION

Determine whether it is under decreased neutrophil production or increased neutrophil destruction: Sequestration

INCREASED NEUTROPHIL DESTRUCTION

Determine whether it is under decreased neutrophil production or increased neutrophil destruction: Pseudo neutropenia

- TOXIC CHANGES

- LEUKOERYTHROBLASTIC REACTION/ LEUKOERYTHROBLASTIC ANEMIA/ LEUKOERYTHROBLASTOSIS

what are the 2 qualitative abnormalities?

TOXIC CHANGES (Morphologic Alterations within the Cell)

- Increased numbers of immature forms (neutrophilic bands and metamyelocytes)

- Left shift

LEUKOERYTHROBLASTIC REACTION/ LEUKOERYTHROBLASTIC ANEMIA/ LEUKOERYTHROBLASTOSIS

- Left shift & circulating nucleated RBCs

- Also happen in hemolytic anemia, uremia, megaloblastic anemia (mild and transitory)

myelophthisis

In LEUKOERYTHROBLASTIC REACTION/ LEUKOERYTHROBLASTIC ANEMIA/ LEUKOERYTHROBLASTOSIS, it is associated with ______________ (Space-occupying lesions in BM)

TOXIC GRANULES

- Stimulation by organisms or antigens

- Large, dark blue-black

- Tendency to cluster within the cell

- Not all neutrophils are equally affected

ribosomal protein

Granulations for toxic granules may represent the precipitation of _________________ or the RNA caused by the metabolic toxicity within the cells

- Distributed throughout cells

- All cells are affected

Describe Alder Reilly Bodies

DÖHLE BODIES

- Cytoplasmic inclusions

- In segmented and band neutrophils

- Closely apposed to the cell membrane

- Pale blue round/ elongated bodies (1-5 µm)

- Can be transient: seen 1-3 days after injury

parallel rows

In DÖHLE BODIES, it consists of ribosomal RNA, arrayed in ______________

Size: 1-5 µm in dm

Cells affected: Segmented & band forms

Transient: Yes

State the size, cells affected of the body and whether it is or not transient: Döhle Bodies

Size: >5 µm in dm

Cells affected: All types of granulocytes

Transient: No

State the size, cells affected of the body and whether it is or not transient: May-Hegglin Bodies

Autophagocytic Vacuoles and Phagocytic Vacuoles

what are the 2 types of CYTOPLASMIC VACUOLATIONS

Autophagocytic Vacuoles

determine the CYTOPLASMIC VACUOLATION:

- Small (1-2 µm)

- Evenly distributed

Phagocytic Vacuoles

determine the CYTOPLASMIC VACUOLATION:

- Large (7-8 µm)

- Not evenly distributed

- Outlined by visible toxic granules

- Due to ingestion

- Septic processes caused by bacteria/fungi

aside from being >5 µm in dm and not evenly distrubuted, what are the 3 other descriptions of Phagocytic Vacuoles?

- Phagocytosis

- Drugs

- Prolonged storage of cells

- Degranulation on exposure to toxins or radiation

what are the 4 causes of CYTOPLASMIC ALTERATIONS?

- Autophagocytosis

- Extracellular material

under the causes of CYTOPLASMIC ALTERATIONS, phagocytosis is one of them, state the 2 examples

- Chloroquine

- Sulfonamides

- Prolonged storage of cells

- Degranulation on exposure to toxins or radiation

under the causes of CYTOPLASMIC ALTERATIONS, drugs is one of them, state the 4 examples

- CYTOPLASMIC DEGRANULATION

- CYTOPLASMIC PSEUDOPODS (Pseudopodia)

- CYTOPLASMIC SWELLING

what are the 3 other cytoplasmic abnormalities?

CYTOPLASMIC DEGRANULATION

- Normal function of activated or injured neutrophils

- Accompanied by cellular membrane destruction

CYTOPLASMIC PSEUDOPODS (Pseudopodia)

- Granule-free protrusions (ameboid in movement)

- Indicative of depressed neutrophil locomotion

- Cytotoxic and bacterial agents

- Prolonged storage in EDTA: causes artifactual pseudopodia

- Toxic neutrophils

in CYTOPLASMIC PSEUDOPODS (Pseudopodia), it can be seen in? (3)

CYTOPLASMIC SWELLING

- There is a swollen or edematous neutrophil

- Osmotic swelling of cytoplasm

- Neutrophilic anisocytosis

Macropolycyte

CYTOPLASMIC SWELLING is also called?

False. there is INCREASED adhesiveness to glass

True or False: in CYTOPLASMIC SWELLING, there is decreased adhesiveness to glass

- PYKNOTIC NUCLEI (Pyknosis)

- NECROTIC / DEAD CELL

- HYPERSEGMENTED NEUTROPHIL (Hypersegmentation)

- TOXIC NUCLEAR PROJECTIONS (Nuclear Projections)

- RINGED NUCLEI (Ring-shaped nuclei)

state the 5 nuclear alterations in MORPHOLOGIC ABNORMALITIES

- Shrunken and dense

- Seen in Cells about to die or dehydrated cell, Septic conditions, and Poor staining or preparation techniques.

describe PYKNOTIC NUCLEI (Pyknosis)

- Rarely seen in fresh specimen

- Nuclei: dense and broken into 2 or more rounded portion

- No evidence of filamentous connections

describe NECROTIC / DEAD CELL

- determine the kind of nuclear alteration:

- Neutrophil is large or normal in size with hypersegmentation

- May reflect Vitamin B12 or folate deficiency

describe HYPERSEGMENTED NEUTROPHIL (Hypersegmentation)

- Hair-like projections seen in band forms (inner side)

- Patients with metastatic CA or after radiation

describe TOXIC NUCLEAR PROJECTIONS (Nuclear Projections)

- Toxic states

- Malignant myeloproliferative disorders

- Early infection

describe RINGED NUCLEI (Ring-shaped nuclei)

False. it does NOT

True or False: Increased numbers of eosinophils (eosinophilia) DOES mean there is a protozoal infection

- Hereditary

- Reactive

- Malignant

quantitative abnormalities in eosinophils can either be? (3)

T-lymphocyte

Eosinophil attraction is ______________________ directed and antibody-dependent

tissue parasite

When eosinophils in quantitative abnormalities appears during parasitic killing, it is provoked by __________________.

PRESENCE OF TISSUE PARASITE

under the action of eosinophils, "it is the response to therapy"

ALLERGIC REACTION

under the action of eosinophils, "it is caused by asthma or hay fever (allergic rhinitis)" and "Results to basophil and mast cell degranulation"

- Hereditary

- Reactive

- Malignant

what are the 3 types of eosinophilia?

Hereditary

under the types of eosinophilia, it is a "Autosomal dominant trait"

Reactive

under the types of eosinophilia, it is a "Parasitic invasion", "Hypersensitivity/allergy", and "Hypereosinophilic syndrome (> 1.5 x 109 /L)"

EOSINOPENIA

- Characteristic finding of acute bacterial infections

- ACTH administration

- Prostaglandins, Eph, glucocorticoids

- DEGRANULATION

- VACUOLATION

- HYPERSEGMENTATION (Hypersegmented Eosinophils)

what are the 3 qualitative abnormalities in eosinophils?

DEGRANULATION

under the qualitative abnormalities in eosinophils, it is the "Most prominent alteration", "Reported if specimen is fresh", and "Myeloproliferative disorders"

stored blood

Eosinophils degranulate in _____________.

HYPERSEGMENTATION (Hypersegmented Eosinophils)

under the qualitative abnormalities in eosinophils, it has 3 or more lobes of eosinophils

Day

Age

Physical activity

Basophilia is NOT affected by these factors:

Immediate hypersensitivity reactions

Hypothyroidism

Estrogen therapy

After exercise

Malignant myeloproliferative disorders (CML)

BASOPHILIA

BASOPENIA

Stress

Acute infections Hyperthyroidism Increased levels of glucocorticoids

After ingestion of a fatty meal

Antigen-related stimulation

Granules of basophils are water soluble which are lost during staining.

DEGRANULATION

MONOCYTOPENIA

Glucocorticoid administration

Overwhelming infections

QUALITATIVE ABNORMALITIES

Immature monocytes in circulation

Monocyte transformation into macrophages

May reflect folate deficiency

Nucleus changed to a long band-like shape

Variant lymphocytes (term of choice)

This term is applied when lymphocytes are found in reactive disorders

Atypical lymphocytes Reactive lymphocytes Virocytes Downey cells Transformed lymphocytes

Other names of variant lymphocyte

VARIANT LYMPHOCYTES

Benign in nature; Normal cells that are altered as a result of a normal response to a stimulus

The chromatin structure and parachromatin is used to distinguish the 3

What is used to distinguish the types of variant lymphocyte

TYPE I LYMPHOCYTES

Plasmacytoid lymphocyte or Türk's irritation cell

TYPE I LYMPHOCYTES

Immunocompetent cells of B-cell origin

TYPE I LYMPHOCYTES

Dense chromatin with small defined areas of parachromatin; Distinct nuclear membrane

TYPE II LYMPHOCYTES

Predominate in IM (IM Cell)

TYPE II LYMPHOCYTES

Chromatin strands not as condensed

TYPE I LYMPHOCYTES

Moderately basophilic Foamy appearance

TYPE II LYMPHOCYTES

Abundant Fried egg or flared skirt appearance Pale with basophilia at periphery

TYPE III LYMPHOCYTES

Transformed/ Reticular Lymphocytes

TYPE III LYMPHOCYTES

Finely reticulated chromatin; Chromatin strands finely dispersed with poorly defined parachromatin

TYPE III LYMPHOCYTES

Abundant May/may not be basophilic Clear perinuclear halo

INFECTIOUS MONONUCLEOSIS (IM)

Other name "kissing" disease