HEMA 1 Review PART 2 - Mikhail Gonong PDF

Preview

Summary

LEUKOCYTES Colorless nucleated cells that circulate in the peripheral blood  main line of defense against foreign invaders such as bacteria, viruses, and other foreign antigens found in the: bone marrow, peripheral blood (transport of leukocytes), tissues Production:  granulocytes: bone marrow ...

Description

LEUKOCYTES  

Colorless nucleated cells that circulate in the peripheral blood main line of defense against foreign invaders such as bacteria, viruses, and other foreign antigens  found in the: bone marrow, peripheral blood (transport of leukocytes), tissues  Production:  granulocytes: bone marrow  leukocytes: bone marrow and lymphoid tissues  classified according to:  presence of granules  nuclear segmentation  function  LEUKOPOIESIS: Production of leukocytes (Myeloid: granulocytes, monocytes/ macrophages) and lymphoid lineage (lymphocytes)

PRESENCE OF GRANULES

CLASSIFICATION OF LEUKOCYTES Granulocytes: neutrophils, eosinophils, basophils Agranulocytes: monocytes and lymphocytes

NUCLEAR SEGMENTATION

polymorphonuclears: multi-lobed or segmented nucleus in mature form mononuclears: single mass of unsegmented nucleus

FUNCTION

phagocytes: neutrophils, monocytes, eosinophils, basophils (phagocytize, engulf, and destroy cells) immunocytes: lymphocytes (antibody production)

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

1

GRANULOPOIESIS  Orderly production of mature granulocytes (NEB)  Usually takes: 14 days from immature/blast stage up to release to the circulation STAGE

CELL SIZE

NUCLEUS

CYTOPLASM

GRANULES

N:C RATIO

ADDITONAL NOTES

MYELOBLAST

15-20 um

Round to oval; reddish purple (occupies most of the cell) Nucleoli: 2 or more Chromatin: Fine; uniformly distributed

Moderate basophilia dark blue to blue

dark blue to blue

4:1

Type 1: no granules Type 2: few primary 1-2% in the bone marrow

Nongranular

PROMYELOCYTE

15-21 um

Round to oval Nucleoli: 2 to 3 Chromatin: slightly coarser than previous

pale blue to basophilic

primary/ azurophilic/ non-specific large prominent reddish purple granules

3:1 to 2:1

production of PRIMARY GRANULES begins and ends at this stage 2-5% in the bone marrow

MYELOCYTE

16-24 um

Round to oval Nucleoli: not visible Chromatin: Coarser and more condensed

Slightly basophilic; tinge of blue along the edges of the cell

secondary/specifi c granules

1:1

Production of SECONDARY GRANULES (become

INDENTED; KIDNEY BEAN SHAPE Nucleoli: Not Visible Chromatin: Moderately clumped; coarser

Pale pink to cream colored to colorless

Primary: Few Secondary:

elongated curved, sausage shaped (S OR C SHAPED) Constricted but no threadlike filament Nucleoli: Not Visible Chromatin: Coarse and clump

Pale blue to pink

Primary: Few Secondary: Abundant

METAMYELOCYTE/ JUVENILE CELLS

STAB/BAND NEUTROPHIL

10-15 um

9-15 um

predominant as cell matures) 10-20% in BM LAST STAGE TO UNDERGO MITOSIS

1:1

15-30% in BM (predominant cell in the BM)

1:1 to 1:2

ONLY IMMATURE CELL THAT IS NORMALLY SEEN IN PERIPHERAL BLOOD

increased than the myelocyte stage

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

2

MATURE CELL

CELL NUCLEUS CYTOPLASM GRANULES ADD. NOTES SIZE Pale pink, 2-5 LOBES connected Primary: Rare  primary 9-15 NEUTROPHIL phagocytizing cell cream-colored by thin filaments GRANULES SUBSTANCES PRESENT Secondary: (**neutral um Most abundant in or colorless Nucleoli: Not visible NEUTROPHILS cationic proteins, Abundant anti-bacterial affinity to Primary: acid hydrolases, acid phosphatase muramidase, proteases, peripheral blood Chromatin: coarse, PINK TO dyes) Elastase, MYELOPEROXIDASE (MPO)  usually increased clumped

ROSE during bacterial VIOLET Secondary: lysozyme, lactoferrin, collagenases, vitamin b12 binding proteins, aminopeptidase infections COLORED GRANULES TERTIARY: ALKALINE PHOSPHATASE; **Henry’s: GELATINASE  Increased during 12-17 BILOBED; connected REDDISHCreamEOSINOPHIL EOSINOPHILS Largerum granules: phospholipase, cathepsin, eosinophil cationic protein, colored; may ORANGE parasitic infections byacid thin hydrolases, filaments peroxidase, + major role in killing parasites) Eosinophil derived neurotoxin, MAJOR BASIC PROTEIN-(color have irregular GRANULES without visible (MBP) borders chromatin (Major Basic  Anti-inflammatory Nucleoli: Not visible Protein) cell Smaller granules: arylsulfatase, peroxidase, acid phosphatase Chromatin: Coarse,  Charcot-Leyden BASOPHILS Specific granules:, Peroxidase, Eosinophilic chemotactic factor A, serotonin, Platelet activating factor, clumped crystals: HEPARIN, PROSTAGLANDINS, HISTAMINE disintegrated eosinophil in secretions/exudates (nasal mucus, pleural fluid, stool) 10-14 um

BASOPHIL

unsegmented, bilobed connected by thin filaments without visible chromatin; RARELY HAS 3 OR FOUR LOBES Nucleoli: Not visible Chromatin: Coarse, clumped

slightly pink to colorless

DARK PURPLE TO BLUE-BLACK GRANULES water soluble; easily disintegrate when stain because of improper fixation, smudge appearance

 Less

phagocytic cell than neutrophil and eosinophil  inflammatory response  Pro-inflammatory cell

MAST CELL     

Tissue basophils SIZE: larger than a basophil NUCLEUS: small and round CYTOPLASM: same with basophil Granules: purple and less soluble than basophils

NEUTROPHIL LS: 9-10 days EOSINOPHIL

BASOPHIL

FUNCTION OF GRANULOCYTES Primary phagocytizing cell Host defense-migration to areas of infection Recogniton and processing of foreign antigens Anti-inflammatory cell ANTI-HELMINTHIC/PARASITIC Phagocytosis Less phagocytic cell than neutrophil and eosinophil

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

3

Pro-inflammatory cell Response to ALLERGIC/HYPERSENSITIVITY REACTIONS

MONOPOIESIS   

Production of: monocytes and macrophages CFU-S  CFU-GM Monocyte: blood, macrophages: tissues

STAGE MONOBLAST

CELL SIZE

NUCLEUS

CYTOPLASM

GRANULES

N:C RATIO

12-20 um

Light blue to gray

None

4:1 to 3:1

PROMONOCYTE / IMMATURE MONOCTE

14-18 um

Light blue to gray

Azurophilic (Burgundy colored)

3:1-2:1

MONOCYTE

14-20 um

Round to oval; may be irregularly shaped Nucleoli: 1-2; may not be visible Chromatin: Fine Irregularly shaped; folded; may have brainlike convolutions Nucleoli: 1-5 Chromatin: Fine to Lacy may be round, HORSESHOE SHAPED, or kidney shaped; often has folds producing “brainlike” convolutions

BLUE-GRAY; may have pseudopods and vacuoles

Many fine azurophilic granules “GROUND GLASS APPEARAN CE”FROSTED

LARGEST CELL IN THE PERIPHERA L BLOOD (irregulary shaped)

Sky blue; may contain ingested material

Azurophilic granules

TISSUE MONOCYTE Liver Bone Brain Skin Connective tissues Kidney Lungs: alveolar mac Spleen: Littoral cells Placenta: Hofbauer cells **dendritic cells-most potent APC

Nucleoli: Not visible Chromatin: fine and lacy; arranged in skein-like strands

MACROPHAGE

15-80 um

Eccentric, kidney or eggshaped, indented, or elongated

FUNCTION OF MONOCYTES AND MACROPHAGES Phagocytosis (bacteria, old cells) HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018 Iron metabolism Antigen presenting cells Production of bioactive molecules

4

LYMPHOPOIESIS 

Production of lymphocytes: bone marrow, lymph nodes, spleen, thymus

STAGE LYMPHOBLAST

CELL SIZE 10-18 um

NUCLEUS Round to oval Nucleoli: 1-2 Chromatin:

CYTOPLASM moderate to dark blue , may stain DEEPER BLUE at the periphery and a LIGHTER BLUE near the nucleus

coarse and clumped

PROLYMHOCYTE

same or smaller than lymphoblast

GRANULES None

MODERATE TO DARK BLUE; non-granular

usually non granular but may contain occasional azurophilic granules

round to oval and slightly indented Nucleoli: not visible Chromatin: dense and clumped

MODERATE TO DARK BLUE, thin rim around the nucleus

absent or few azuorphilic granules

round to oval; slightly indented Nucleoli: 1-2

Chromatin: coarser and more clumped than lymphoblast

N:C RATIO 4:1

decreased than previous stage

MATURE LYMPHOCTE **Difference is cell size and cytoplasm; T and B cells can’t be differentiated clearly

SMALL LYMPHOCYTE

8-10 um (approximately the size of an RBC)

“ROBIN’S EGGG BLUE”

MEDIUM LYMPHOCYTE

10-12 um

Round to oval and slightly indented Nucleoli: not visible Chromatin: clumped but not as dense as a smally lymphocyte

more abundant in small lymphocyte; PALE TO MODERATE BLUE

absent or few azurophilic granules

LARGE

12-16 um

round to oval and slightly indented;

abundant; clear and VERY PALE

absent or few azurophilic

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

5

may be eccentrically located Nucleoli: Not visible Chromatin: coarser

LYMPHOCYTE

TYPES OF MATURE LYMPHOCYTES T-CELLS B-CELLS NULL LYMPHOCYTE/ NK CELLS

STAGE PLASMABLAST PROPLASMACYTE PLASMACYTE/PLASMA CELL

PERCENTAGE 60-80% 10-15% 10%

BLUE

FUNCTION Cellular immunity Humoral immunity Tumor and viruses (TNF)

CELL SIZE 18-25 15-25 8-20

NUCLEUS Eccentric (off center) Eccentric Eccentric *CARTWHEEL APPERANCE

granules

ORGANS PRESENT Thymus Bone marrow Bone marrow

SURFACE MARKERS CD2, CD4, CD8 CD10,CD19,CD24 CD16, CD56, CD94

CYTOPLASM Basophilic, Non-granular Intensely basophilic, Non-granular Deeply basophilic, Non-granular HOF/perinuclear halo

WBC MORPHOLOGICAL ABNORMALITIES CYTOPLASMIC ABNORMALITIES: 1. TOXIC GRANULES  Color: Large purple to black granules (dark granulation)  May be present in: band/segmented neuts, monocytes  primary/azurophilic granules are larger than secondary granules  PAS reaction: (PAS +); precipitation of rRNA  Associated with toxic vacuoles (can be associated. with autophagocytosis)  Clinical significance: infections, toxic states 2. DOHLE-BODIES/ DOHLE-AMATO BODIES  Color: Pale blue inclusions in the cytoplasm  Composition: composed of rRNA- ribosomes of RER  May be present in: segmented/band neutrophils  PAS reaction: positive  Confused with May-Hegglin bodies (PAS negative)

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

6

 Localized failure of cytoplasmic maturation  Clinical significance: severe infections, toxic states, burns 3. MAY-HEGGLIN GRANULES  Color: Gray-blue spindle shaped inclusions in the cytoplasm  Composition: Composed of mRNA  Presence of: giant platelets (abnormal platelets= lack dense granules)  Resembles Dohle bodies (smaller)  Clinical significance: infections, Thrombocytopenia, leukopenia, May-Hegglin anomaly **BSS 4. CHEDIAK-HIGASHI GRANULES  Color: Giant red, blue, to grayish round inclusions in the cytoplasm (giant lysosomal granules)  Disorder:  Deficiency in enzymes in the lysosomes required for phagocytsosis (lysosomal defect)  Poor chemotactic activity (poor directional motility)  Clinical significance: Chediak-Higashi syndrome (autosomal recessive), Albinism 5. ALDER-REILLY GRANULES/BODIES  Color: Purple-Red  Abnormal large primary granules  Accumulation of: degraded mucopolysaccharides  May resemble toxic granules (seen in infections and toxic states)  May be found in all leukocytes with DENSE GRANULES  Clinical significance: Alder-Reilly anomaly (autosomal recessive), Mucopolysaccharidoses, hunter’s syndrome, Hurler’s syndrome 6. AUER RODS  Color: Pink or red shaped cytoplasmic granules; found in myeloid and monocytic series only  Fused primary granules (peroxidase stain positive)  Faggot cells: bundle of auer rods (seen in acute promyelocytic leukemia; M3; also associated with DIC)  Clinical significance:  Acute myelogenous leukemia (AML, M1 and M2)  Acute promyelocytic leukemia (APL, M3)  Acute myelomonocytic leukemia (AMML, M4)

NUCLEAR ABNORMALITIES 1. HYPERSEGMENTED NEUTROPHIL  Neutrophil has more than 5 lobes  Abnormal DNA synthesis  Clinical significance: Undritz anomaly (hereditary), megaloblastic anemia (acquired) 2. PELGER-HUET  Hyposegmentation of granulocyte nucleus (single or bilobed)  “Pince-nez appearance”, dumbbell, peanut (heterozygous), round shaped nucleus (homozygous)  Hyposegmentation can also be caused by shift to the left  Clinical significance: Preleukemia/ Myelodysplastic syndromes, Pseudo pelger-Huet (seen in myeloproliferative disorders; CML), Pelger-Huet anomaly 3. LE CELL  Neutrophil with large purple homogenous round inclusion with engulfed nucleus of another cell (usually another neutrophil)

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

7

 Presence of: ANTI-NUCLEAR ANTIBODIES, cell nuclei, phagocytes with ingested material  Usually mistaken with a tart cell (monocyte with an ingested lymphocyte)  Clinical significance: Systemic Lupus Erythematosus 4. BARR BODY (SEX CHROMATIN)  Represents the: 2nd X chromosome in females  Seen in: 2-3% of neutrophils  Apperance:” DRUMSTICK”

LYMPHOCYTE ABNORMALITIES: 1. BASKET CELL/SMUDGE CELL  Associated with: Degenerated nucleus or ruptured cell in form or basket/smudge  THUMBPRINT APPEARANCE  FRAGILE LYMPHOCYTES that appear during smear preparation (ARTIFACT; appear at the end of smears)  Clinical significance: Chronic Lymphocytic leukemia 2. HAIRY CELL  Hair like cytoplasmic projections surrounding the nucleus (fried-egg appearance)  Positive with: TRAP stain (Tartrate-resistant acid phosphatase stain)  Clinical significance: Hairy cell leukemia 3. SEZARY CELL  Round lymph cell with: convoluted nucleus (brain-like nucleus)  Presence indicates LEUKEMIC PHASE of mycosis fungoides (sezary syndrome)  Clinical significance: Mycosis fungoides (cutaneous T-cell lymphoma), Sezary syndrome (variant of mycoses fungoides) 4. REED-STERNBERG CELLS  Apperance: “owl’s eye appearance”  Pathognomonic sign for HL  Clinical significance: Hodgkin’s Lymphoma

5. RIEDER CELL  Lymphocyte with a: clover leaf like nucleus  Clinical significance: Chronic lymphocytic leukemia 6. REACTIVE/VARIANT/ATYPICAL LYMPHOCYTE  T-cells reacting to B-cells infected with Epstein-Barr virus (EBV)  Clinical significance: infectious mononucleosis  Aka: “downey cells”  Types of downey cells:  Type I: turk’s irration plasma cytoid; lymphocyte with a large block of chromatin  Type II: also known as IM cells; round mass of chromatin (ballerina skirt appearance)  Type III: vacuolated (swiss cheese appearance) 7. FLAME CELL  Plasma cell with: red to pink cytoplasm  Associated with increased Immunoglobulins (usually IgA);

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

8

 

Inclusion: russel bodies (individual bodies of Immunoglobulin) Clinical significance: Multiple myeloma, Waldenstrom’s macroglobulinemia

8. GRAPE CELL (Mott cell/Berry cell/Morula cell)  Plasma cell with small colorless vacuoles  Inclusions: Dutcher’s bodies (intranuclear protein inclusions)  Large protein globules giving appearance of grapes: “Honeycomb appearance”  Clinical significance: Multiple myeloma; reactive states

MACROPHAGE ABNORMATILIES 1. GAUCHER CELLS  Within the BM; large macrophages: with crumpled tissue paper appearance  Cytoplasm onion skin like appearance  Clinical significance: Gaucher’s disease (def. in the enzyme glucocerebrosidase or beta-glucosidase) 2. FOAM CELLS  Macrophages whose cytoplasm is filled with small lipid droplets; FOAMY CYTOPLASM  Clinical significance: Niemman Pick’s disease (def. in the enzyme acid sphingomyelinase)

HEREDITARY NON-MALIGNANT WBC DISORDERS

INHERITED ABNORMALITIES OF GRANULOCYTE MORPHOLOGY: NUCLEAR ABNORMALITIES: 1. PELGER-HUET ANOMALY  Hyposegmentation of the granulocyte nucleus with increased density and coarseness  Two types: “True” (inherited) and “Pseudo” (acquired)  True Pelger-Huet anomaly is autosomal dominant  Heterozygous: pince-nez, dumbbell shaped, peanut shaped nucleus  Homozygous: round nuclei  Pseudo Pelger-Huet o Associated with: malignant myeloproliferative disorders, Preleukemia/myelodysplastic syndromes 2. HEREDITARY HYPERSEGMENTATION OF NEUTROPHILS

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

9

 

Autosomal dominant: (undritz anomaly) Also associated with: Vitamin B12 deficiency (acquired)

3. BARR BODY (SEX CHROMATIN)  Represents the 2nd X chromosome in females  Seen in: 2-3% of neutrophils  Apperance:” DRUMSTICK”

CYTOPLASMIC ABNORMALITIES: 1. MAY-HEGGLIN ANOMALY  Characterized by: leukopenia, thrombocytopenia, GIANT PLATELETS (hypogranular), with GRAYBLUE SPINDLE-SHAPED INCLUSIONS in the cytoplasm of granulocytes and monocytes  Granules are made up of: mRNA  Autosomal dominant  Prolonged BT and abnormal clot retraction, normal platelet aggregation studies (ACE) 2. ALDER-REILLY ANOMALY  Abnormal morphology: LARGE AZUROPHILIC GRANULES REMBLING TOXIC GRANULES  Associated with: Mucopolysaccharidoses ABNORMAL MOVEMENT: 1. JOB’S SYNDROME  Normal: random movement  Abnormal: CHEMOTACTIC/DIRECTIONAL MOTILITY IS IMPAIRED  Patient suffer from PERSISTENT BOILS and recurrent “cold” STAPHYLOCOCCAL ABSCESSES  Associated with increased IgE 2. LAZY LEUKOCYTE SYNDROME  Abnormal: Both random and chemotactic movement of the cells are defective  Cells failed to respond to inflammatory stimuli but have normal phagocytic and bactericidal activity

DEFECTIVE KILLING OF MICROORGANISMS (X OXIDATIVE BURST) 1. CHEDIAK-HIGASHI ANOMALY  Presence of abnormal: giant cytoplasmic granules in phagocytes (Peroxidase +) and lymphocytes (-)  Defect:  DEFECTIVE GRANULE RELEASE into phagosomes which results to poor bacterial killing  Lysosomal granules are normal in content but are abnormally packaged  POOR CHEMOTACTIC/DIRECTIONAL MOTILITY; lymphocytes lacks natural killer activity  Associated with: partial albinism and recurrent infections 2. CONGENITAL C3 DEFICIENCY  Autosomal recessive  Heterozygous: carriers have half the normal C3 activity (adequate for disease resistance)  Homozygous: repeated severe infections with encapsulated bacteria which are poorly recognized and inefficiently phagocytized because of failure of opsonisation by C3 3. CHRONIC GRANULOMATOUS DISEASE (CGD)

HEMATOLOGY REVIEW I OLFU-PAMPANGA I M.K.S.G 2018

10

  

Abnormality: impaired oxidative burst (X NADPH oxidase) INCREASE IN OXYGEN UPTAKE and generation of oxygen metabolites Evaluation of respiratory burst: o Chemiluminescense o Nitroblue tetrazolium (NBT) test  NBT is a yellow, water-soluble dye  Normal: REDUCED NBT because of respiratory burst (+BLUE FORMAZAN)  CGD: UNREDUCED (COLORLESS-YELLOW)

4. G-6-PD DEFICIENCY  Absence affect the: HEXOSE MONOPHOSPHATE SHUNT  Abnormality: UNABLE TO PRODUCE A RESPIRATORY BURST, resulting in a DEFECTIVE BACTERICIDAL ACTIVITY  G6PD is needed for the production of NADPH oxidase 5. MYELOPEROXIDASE DEFICIENCY  Autosomal recessive  MPO is absent in neutrophils and monocytes but not in eosinophils  Absence of MPO: slows down bactericidal killing...