Week 2 Flashcards
Age related quantitative differences in CBC results - Newborn Population
-Neutrophil and Lymphocyte ratio change as you age
-NB have higher WBC count, Neut % and absolute count
-as the child reaches 1 the % of lymphs doubles the amount of neutrophils = reverse ratio or inverted diff (37-73)
-in grade school the values will go the values as an adult (18-42 of lymph)
-baby lymphs can be seen and can be mistaken for blasts
Age related quantitative differences in CBC results- Geriatric Population
-cbc only a little different from younger adults
->65 yrs slightly lower WBC, RBC, HGB and PLTs and slightly high MCV
-due to decline in physical activity and reduce BM output, and various disease
-cells lose the ability to divide as you get older
-production of hematopoiesis reduced from 50-30% due to bone loss and increased fat stores
What happens to the immune response as you age
what are you more prone to
-reduced signaling - lymphs and neuts (phagocytosis, chemotaxis)
-loss of thymus so the body is dependent on memory and tissue T cells
-T cells regulate B cells = less AB production, making the person more susceptible to infections
anemia -
IDA (ulcers, or NSAIDS) and Megaloblastic (b12 def) - gastro issues
Anemia of chronic disease (RA)
cancers
Leukemias
Quantitative Neutrophil Changes
Absolute Neutrophilia
when its benign and when its pathological
Benign
Neuts are shifted from Marginal to circulatory pools
-caused by stress, trauma, excercise, shock , burns and an increase in epinephrine
Pathological conditions
Neuts are shifted from Marginal to circulatory pools
-increase in BM production in Neuts series
-neuts released from Storage pool to PB
-infection
-LEFT SHIFT = PRESENCE OF IMMATURE NEUTS
What is left shift
- increase in immature cells like bands, metalyelocytes or myelocytes as indicator of INFECTION as part of WBC differential
-increased release from storage pool
-seen with neutrophilia and toxic changes
-toxic changes refers to cytoplasmic basophilia , dohle bodies , heavy cytoplasmic vacuoles, heavy course granules
What is a leukemoid reaction
-leukocytosis above 50 x10^9 with neutrophilia and MARKED left shift
-bands, metas/myelos,
pro or blasts in PB
*confused with CML
-increased in all granulocytes especially eos and basos , platelets are increased early and drop later, Pseudo Pelger Huet forms, low hgb, HCR-BAL gene positive, low LAP
- LR are just increased in just neuts, normal plts, hgb , see granulation and Dohle bodies, increased LAP
result of
-severe or chronic infections like TB or pneumonia
-metabolic disease
-inflammation
-responding to a malignancy
What is a leucoerythroblastic picture
-when there are immature neuts, nucleated RBCs (immature erythrocytes) and teardrops in the same same
-this reaction shows that there might be a lesion in the bone marrow : metastatic tumor, fibrosis, lymphoma, leukemia, marked increase in BM cells (erythroid hyperplasia in HA)
-sometimes there is neutrophilia but not always
-associated with primary myelofibrosis
What causes absolute neutropenia
abnormally reduced count in PB
1.high rate of removal or destruction of PB neutrophils
2.low production and ineffective hematopoiesis (neuts are present in BM but not released because they are defective)
3.low ratio of CP vs MP
3.BM storage pool is depleted
4. BM suppression - low production/impaired release like acute leukemia and aplastic anemia
-overwhelming infection - using too much during infection - bad prognosis
What is eosinophila
absolute count >0.4 x10^9
-nonmalignant increase caused by cytokine causes
Allergies- asthma
Parasitic infection
Autoimmune disorder HIV
Fungal infections
Malignancies
What is basophilia
absolute count over >0.15 x10^9/L
non malignant causes
-bee sting
food and drug HYPER sensitivity
-chronic infections
-hypothyroidism
-chronic inflammation
-radiation therapy
Malignant myeloproliferative neoplasms
-chronic myelogenous leukemia - CML
Qualitative Granulocyte abnormalities are characterized by morphological changes in
Nucleus and/or cytoplasm
Acquired or inherited
how would you describe the nucleus and cytoplasm in acquired granulocyte alterations and abnormalities
Nucleus
Hyposegmentation
Hypersegmentation
Pyknotic (irreversible condensation in the nucleus in a cell undergoing apoptosis) and Necrobiotic (remaining nuclear material of a dead cell) forms
Cytoplasm
Toxic granulation
Degranulation
Vacuolization - with/out engulfed matter
Dohle bodies
Acquired qualitative nuclear disorders
Nuclear abnormalities
Hyper seg - over 5 segments
Chronic infections
MA
Drugs
Hypo segmented - bi-lobed or no segmentation
Myelodysplastic syndromes
Asynchrony of nuclear maturation - clumped chromatin and no segmentation
Myelocyte vs hyposegmentation
if myelocytes - since they are a stage in maturation only some should be myelocytes
if most look the same then they could be hyposegmentation
look at all cells
are they the same
are they mature and hyposegmented or are they early
look at granules and chromatin
chromatin is clumped with 2ndart granules = mature hyposeg neut
in inherited conditions all cells are hyposegmented
pyknotic vs necrotic
Pyknotic
-dying cell
-dark/dense nucleus
-visible filaments
Necrotic
-dead cell
-round fragments of nucleus
-no filaments
Nuclear abnormalities
Mitotic cells
-only seen in BM
-not abnormality just a phase in cells life
-only comment if several are seen
-dont count in DIFF because the stage cant be identified because the nucleus is getting ready to divide
Acquired Qualitative Cytoplasmic Disorders
what do you look at
-absence of granules
-hypo or a granular
-degranulation
abnormal granules with abnormal function
Toxic changes in neutrophils
Cytoplasmic abnormalities
reactive morph changes in neuts include toxic granulation, Dohle bodies, and cytoplasmic vacuoles
-considered abnormal changes but reflect a normal reactive response when neuts respond to infection
What is toxic granulation
Cytoplasmic abnormalities
stress response to infection/inflammation
-significant marker of inflammation
report with WBC morph
occ/some/many
What is toxic vacuolization
Cytoplasmic abnormalities
-when neuts have several vacuoles
-seen with toxic granulation
-spontaneous
-indicates phagocytosis
-may contain bacteria
-clinically significant
report with WBC morphology
occ/some/many
determine the difference btwn autophagocytotic vacuoles due to housekeeping (small and even) and autophagocytotic vacuoles due to infection
What are dohle bodies
Cytoplasmic abnormalities
Pale blue, oval inclusions at periphery
-grey/blue on Wright stain
-only in neutrophils
Remnants of rRNA
Associated with
-Bacterial infection
-Sepsis
-Pregnancy
Report with WBC morphology
Occ/some/many
What is the LE phenomenon
Cytoplasmic abnormalities
LE cell
Lupus Erythematosus cell
Mature neut that has phagocytized a round even inclusion
-the inclusion is the nuclear material of degenerating leukocytes that are coated with ANA
-not seen in PB unless manipulated with small glass beads that exposes the nucleus to the ANA which then coats them and are engulfed by the neuts
-after the neut engulfs the nucleus the protein in the nucleus is depolymerized by the AB= appears homogenous
-found with SLE and autoimmune conditions
-ANA blood test replaced the cell test
-seen in fluids -synovial fluids its natural - trauma needed to expose the nucleus is also present
Auer Rod
Cytoplasmic abnormalities
-not non malignant change
-early clue for the type of leukemia
-seen in Leukemia - blasts and promyelocytes
-only in myeloblasts not lymphoblasts so it seen you can conclude the pt has acute myeloid leukemia and not acute lymphoid leukemia
Fused primary granules
-Azurophilic rods
DONT CONFUSE WITH DOHLE BODIES
report with WBC morph
occ/some/many
Inherited Qualitative Abnormalities
Pelger Huët Anomaly
hyposegmentation of neutrophil nucleus
-autosomal dominant
-asymp
-70-90% of neuts are affected
heterozygous state
-bilobed nucleus
-dense heterochromatin (mature cell)
-incomplete nuclear segmentation
-dumbbell or pince nez
Homozygous state
-nucleus is round or oval
-no segmentation
can be confused with band or myelocyte due to coarse and dense chromatin
Inherited Qualitative Abnormalities
Alder-Reilly Anomaly
Autosomal recessive
-abnormally large metachromatic granules in cytoplasm of granulocytes, monocytes and lymphocytes
-incomplete degradation of mucopolysacc
-mucololysaccs deposit granules in most cells
-people who have this anomaly dont have the enzymes that digest the mucopoly in lysosomes so they deposit into the cells
-heavy granulation = purple or lillac
-sometimes only one cell line is affected
-looks like promyelocytes or heavy toxic granulation
leukocyte function is not affected
Inherited Qualitative Abnormalities
May-Hegglin Anomaly
Autosomal Dominant (rare)
Platelet Disorder - giant and hypo granular
Characterized by Variable thrombocytopenia with giant platelets and Leukopenia with large basophilic inclusions in Neut, Eos Baso and Mono
Inclusions look like Döhle bodies in except:
Seen in all granulocytes & monocytes
Made up of precipitated myosin heavy chains
Larger than Dohle bodies in infection and permanent, not transient
Not seen with other toxic changes
pts are asymp or have mild bleeding disorder- related to degree of thrombocytopenia
Inherited Qualitative Abnormalities
Chediak-Higashi Syndrome
Autosomal Recessive
Rare, fatal
-characterized by abnormal fusion of granules -large and mostly dysfunctional in all WBCs
-Hematopoietic cells are affected
-Disease manifestations can be found in hair, skin, adrenal and pituitary glands, and nerves
The fused granules results in
-Dysfunctional phagocytosis & inefficient bacterial destruction, increased disease susceptibility like staph infections- albino
-Affect Platelet dense granules that contain ADP resulting in increased Tendency to bleed
-Affected granules in Melanocytes: albinism
-neurological issues from childhood
What is pseudo pelger huet
- drug induced
-in pt with HIV , TB, Mycoplasma pneumonia, bacterial infections
2ndary to myelodysplastic syndromes
True vs Pseudo Pelger Huet
True - all WBCs affected in nuclear shape and chromatin
-hyposegmentation
Fake - only in neuts with other changes like neutrophilia and toxic changes
In comments report- Pelger huet forms if all neuts are affected - bi lobed or singled lobed
under WBC morph quantify as : hypersegmented neuts if they look dysplastic so mature chromatic with no segmentation
Chronic Granulomatous Disease
-Rare X-linked or Autosomal Recessive
-normal Neutrophil Morphology but functionally abnormal
-phagocytes cant produce NADPH oxidase (kills microorganisms)
-can phagocytize but cant kill
-Bacteria are not killed on ingestion encased in granulomas - localize bacteria. When they rupture, itll release live bacteria and pus
causing -Recurring bacterial & fungal infections
Chronic Granulomatous Disease
Morphology
hard to diagnose on PBS alone
Normal WBC morph or Neutrophilia with toxic changes (like in bacterial infection)
Diagnose with :
Use Nitroblue tetrazolium reduction test:
Normal neuts when stimulated able to produce reactive oxygen species and are able to reduce yellow to dark blue. However disease neuts cannot so the tetrazolium remains yellow = disease
-Use flow cytometery with use of fluorescent probes to measure intracellular production on NADPH oxidase
-or genetics
Macrophage-rich granulomas can be found in the liver, spleen, and other organs. These granulomas sometimes obstruct the intestines, urinary tract, and lungs
How to tell the difference between toxic granulation and Alder Reilly
Neutrophilia, Dohle bodies and left shift = toxic granulation not with Alder Reilly
In Alder-Reilly = granules can be found in lymphocytes and monocyte whereas in toxic granulation they are found in neutrophils
