WBC disorders B4 Flashcards
Growth factors:
KIT ligand & FLT3 ligand are ________ growth factors
Stem cell growth factors
Growth factors:
What are the 2 Stem cell growth factors
KIT & FLT3 ligands
List the progenitor cell line for Stem cells
1) Hematopoietic stem cell
2) Multipotent progenitor
Growth factors are KIT & FLT3 ligands
List the progenitor cell line for Myeloblasts (3 paths)
Basophil path:
1) Myeloid stem cell (Bone marrow)
2) Myeloblast (CD33/34 neg & CD13/15 pos)
3) Immature Basophil
4) Basophil
Eosinophil path:
1) Myeloid stem cell (Bone marrow)
2) Myeloblast (CD33/34 neg & CD13/15 pos)
3) Immature Eosinophil
4) Eosinophil
Neutrophil path:
1) Myeloid stem cell (Bone marrow)
2) Myeloblast (CD33/34 neg & CD13/15 pos)
3) N. Promyelocyte
4) N. Myelocyte
5) N. Band
6) Neutrophil
growth factor is G-CSF
List the progenitor cell line for Monocytes
1) Myeloid stem cell (Bone marrow)
2) Immature monocyte
3) Monocyte
growth factor is GM-CSF
List the progenitor cell line for Platelets
1) Myeloid stem cell (Bone marrow)
2) Megakaryocyte
3) Platelets
growth factor is thrombopoietin
List the progenitor cell line for RBC’s
1) Myeloid stem cell (Bone marrow)
2) Pro-Normoblast
3) Basophilic Normoblast
4) Polychromatic Normoblast
5) Orthochromatic Normoblast
6) Polychromatic Erythrocyte
7) Erythrocyte
growth factor is Erythropoietin
List the progenitor cell line for Lymphocytes
1) Myeloid stem cell (Bone marrow)
2) Lymphoid stem cell (Lymph nodes)
3) Lymphocyte
Describe how corticosteroid can cause Eosinopenia, Lymphopenia & Neutrophilia
1) Corticosteroids trap eosinophils in the lymph nodes
2) Corticosteroids induces apoptosis in lymphocytes
3) Corticosteroids increase neutrophil release from bone marrow & decreases neutrophil adhesion molecules, so they don’t stick to the walls of blood vessels and can’t move out of the circulation
What are the 3 main side effects on blood WBC counts that happen with corticosteroid use
Eosinopenia
Lymphopenia
Neutrophilia
Describe how Cushing’s can cause leukopenia & eosinopenia
Excessively high levels of ACTH or cortisol trigger leukopenia and eosinopenia
How does Cushing’s impact WBC counts?
Eosinopenia
Lymphopenia
Proliferative WBC disorder with too many leukocytes
Leukocytosis
WBC disorder with too few leukocytes
Leukopenia
Agranulocytosis means there are
to few neutrophils (under 500) this can cause severe infections!
WBC with eosinophils under 30
Eosinopenia
List the normal WBC labs for:
Leukocytes
4500-to-11,000
List the normal WBC labs for:
Segmented neutrophils
54-62%
List the normal WBC labs for:
Bands
3-5%
List the normal WBC labs for:
Eosinophils
1-3%
List the normal WBC labs for:
Basophils
0-0.75%
List the normal WBC labs for:
Lymphocytes
25-33%
List the normal WBC labs for:
Monocytes
3-7%
Blast cells in the serum likely indicate what?
Leukemia
Patient presents with:
Low grade fever
WBC count of 80,000
Chronic cough
Elevated monocyte count
It likely indicates what?
Chronic inflammation
Increased Bands in the serum likely indicate what?
An acute infection with a leftward shift
List some common causes of Lymphopenia
1) Congenital immune deficiencies (Di George syndrome, HIV, AIDS, & SCID)
2) Post treatment with glucocorticoids or cytotoxic drugs
3) Autoimmune disorders
1) Congenital immune deficiencies (Di George syndrome, HIV, AIDS, & SCID)
2) Post treatment with glucocorticoids or cytotoxic drugs
3) Autoimmune disorders
Are all common causes of what disordered WBC level?
Lymphopenia
Neutropenia is described as having what level of serum neutrophils?
WBC disorder with an absolute neutrophil count < 1500
Describe the possible causes of Neutropenia
1) Decreased production of granulocytes (aka poor granulopoiesis)
2) More destruction or sequestration of neutrophils (aka less neutrophils are released into blood)
3) Drug reactions with either Chloramphenicol (causes aplastic anemia) or Chlorpromazine (an antipsychotic sedative) both are toxic to the bone marrow and mess with granulopoiesis
Describe the common causes of agranulocytosis (neutrophils <500)
Drugs toxicity to the bone marrow (Chloramphenicol, Chlorpromazine, Sulfonamides, Thiouracil, & Phenylbutazone)
Describe how drug toxicity to Sulfonamides can lead to agranulocytosis
The sulfonamide causes the body to make antibodies against our own neutrophils (very similar to immune hemolytic anemias)
Describe the signs of agranulocytosis (Neutrophils <500)
Ulcerating necrotic lesions in the mouth, gingivae, & pharynx that are covered by a gray-green-black necrotic membrane with lots of bacteria/fungi but little to no leukocyte response
Patient has the following, what is the condition?
agranulocytosis (Neutrophils <500)
Leukocytosis (increased WBC #) is primarily dependent on 4 factors
1) The number of myeloid and lymphoid precursors and storage pools
2) The rate of cell release from storage
3) The percentage of marginating WBCs
4) The rate of extravasation (aka leaving blood-to-tissues)
1) The number of myeloid and lymphoid precursors and storage pools
2) The rate of cell release from storage
3) The percentage of marginating WBCs
4) The rate of extravasation (aka leaving blood-to-tissues)
Impact what component within blood labs
Leukocytosis
Describe how increased bone marrow in response to ________________________________causes leukocytosis
1) Chronic infection/inflammation (dependent on GF)
2) Paraneoplastic syndromes (dependent on GF)
3) Myeloproliferative disorders (independent of GF)
Describe how more release of leukocytes from storage in response to ________________________________causes leukocytosis
1) Endotoxemia
2) Infection
3) Hypoxia
Describe how a decreased marginating pool of WBC’s in response to ________________________________—–causes leukocytosis
Exercise & catecholamines
Describe how a decrease in extravasation of WBCs going into tissues in response to ________________________________—–causes leukocytosis
Glucocorticoids (aka corticosteroids)
What can stimulate neutrophilic leukocytosis
It can be stimulated by any stress (both catecholamines & glucocorticoids)
Neutrophilic leukocytosis can be caused by what conditions
1) Acute bacterial infections
2) Sterile inflammation
3) Tissue Necrosis
Eosinophilic leukocytosis (eosinophilia) can be caused by what conditions
1) Allergic disorders
- asthma
- hay fever
- parasitic infestation
2) Certain malignancies
- Hodgkin & some non-Hodgkin lymphoma
3) Some vasculitides
4) Atheroembolic disease
5) Polyarteritis nodosa
Basophilic leukocytosis (Basophilia) can be caused by
rare myeloproliferative disease (chronic myelogenous leukemia)
Monocytosis can be caused by
1) Chronic infections (Tuberculosis)
2) Bacterial endocarditis
3) Rickettsiosis
4) Malaria
5) Autoimmune disorders (SLE)
6) Inflammatory Bowel Disease (Ulcerative colitis)
Lymphocytosis is associated with what?
1) monocytosis in many chronic immunological stimulation (ex. 2)Tuberculosis Brucellosis)
3) Viral infections (Hep A, CMV, EBV)
4) Bordetella pertussis infection
Describe the features highlighted in the histo slide
Dohle bodies (fragmented ribosome-rich endoplasmic reticulum with a “sky-blue puddle appearance”) Usually only seen in SEVERE septic or inflammatory conditions.
&
Toxic granulations
Describe the features of sepsis & Severe inflammatory disorders (leukocytosis)
1) Neutrophil count is 60,000 (very high)
2) Neutrophils have Dohle bodies, Cytoplasmic vacuoles, & toxic granulations (coarse + dark granules)
Which conditions are NOT associated with eosinophilia (aka their non-invasive)
Pinworms & Adult ascariasis
IL-5 mainly stimulates what?
Eosinophil production
Describe leukemoid reactions
Involved with severe infections & very high WBC count >50,000 it mimics myeloid leukemia (but it’s NOT)
1) Increased mature neutrophils
2) Fewer immature neutrophils
3) Neutrophils have high levels of LAP (Levels of Alkaline Phosphate)
4) Neutrophil production is normal and they show
- positive CD13/CD15
- negative CD33/CD34 & HLA-DR
How can you tell the difference between leukemoid reactions & malignant WBC’s
Myeloid leukemoid has LAP
Malignant WBC’s don’t have LAP (ex. CML)
Pancreatitis presents with what?
Neutrophilic leukocytosis with inflammation
Common leukemoid reactions include what conditions?
1) Pancreatitis
2) Infectious pneumococcal pneumonia
3) Neoplastic carcinoma of the lung
4) Perforated appendicitis
Describe the following features of this histo slide
Normal neutrophils with high levels of LAP making this a leukemoid reaction
Describe the following features of this histo slide
Malignant neutrophils with absent/very low levels of LAP
Describe the features of acute non-specific lymphadenitis
Antigens cause the primary follicles to enlarge & develop pale germinal centers (where B cells make Abs vs those antigens)
The paracortical T-cell zones can also enlarge
Antigens cause the primary follicles to enlarge & develop pale germinal centers (where B cells make Abs vs those antigens)
The paracortical T-cell zones can also enlarge
features of acute non-specific lymphadenitis
Describe the features of lymphadenitis
The lymph nodes are enlarged/painful & the overlying skin is red (soft/fluctuant if there’s an abscess)
Suppurative infections can penetrate through the capsule of the node & can track to the skin causing draining sinuses that scar after healing
Acute lymphadenitis histology can be described as
1) Big reactive germinal centers with many mitotic figures
2) Macrophages have granulation from dead bacteria or necrotic cells
First the neutrophils are prominent then the follicle centers become necrotic
Cervical lymphadenitis is usually from infected ______&________
Teeth & Tonsils
Axillary or inguinal lymphadenitis is usually from infections to _________
infections in the extremities
Acute lymphadenitis in the mesenteric lymph nodes drain to form _____________
Acute appendicitis
Describe the features of non-specific acute lymphadenitis
Foci of necrosis (the arrowhead) and acute inflammatory cells (presence of neutrophils) the arrow line
Describe the features of chronic non-specific lymphadenitis
In chronic reactions lymph nodes (ex. supraclavicular or inguinal nodes commonly affected) are non-tender & enlarged it happens slowly over time with no associated tissue damage
Describe the features of follicular hyperplasia
1) Has discrete & well-defined separated follicles with intrafollicular tissues
2) Follicles are varied in size/shape
3) Have well-defined mantle zones
4) Heterogeneous population of follicle center cells (large cells outnumber small cells in large follicles which are mitotically active)
5) bcl-2 staining is NEGATIVE in the germinal centers
Malignant nodules stain __________ for bcl-2 and indicate what?
bcl-2 positive & indicate follicular lymphoma
What conditions are commonly associated with follicular hyperplasia
- Rheumatoid arthritis
- Toxoplasmosis
- Early stages of infection of HIV
Describe the histological signs of follicular hyperplasia
There’s large oblong germinal centers (secondary follicles) surrounded by a collar of small resting naive B cells (mantle zones)
Describe the following features in the histological slides
follicular hyperplasia:
- germinal centers (secondary follicles)
- a collar of small resting naive B cells (mantle zones) that surround the follicles
- several mitotic figures
- numerous macrophages containing phagocytosed apoptotic cells (tangible bodies)
Describe the features of paracortical hyperplasia
A large of number of T-cell indicates a viral infection (stims T-cell response) such as:
- Herpes simplex virus
- Epstein barr virus (infectious mononucleosis)
- Cytomegalovirus
Describe the following features on the slide
Acute lymphoblastic leukemia/lymphoma
Lymphoblast’s with condensed nuclear chromatin, small nucleoli, and scant agranular cytoplasm.
Compared with myeloblasts, lymphoblast’s have more what?
1) Condensed chromatin
2) Poorly visible nucleoli
3) Smaller amounts of cytoplasm that usually lacks granules.
Hyperplasia’s:
Describe the features of follicular hyperplasia
The follicles are discrete, well-separated, vary in size/shape, & have well-defined mantle zones
&
BCL-2 Negative germinal centers
Tangible bodies
Describe the condition and the visible features on the histo slide
Follicular hyperplasia with tangible bodies
A condition where:
The follicles are discrete, well-separated, vary in size/shape, & have well-defined mantle zones
&
BCL-2 Negative germinal centers
Tangible bodies
Follicular hyperplasia
Hyperplasia:
Describe the features of paracortical hyperplasia
When stimulus triggers T-cell med immune responses (high # of Tcells = VIRAL INFECTION)
ex EBV, HSV, CMV
When stimulus triggers T-cell med immune responses (high # of Tcells = VIRAL INFECTION)
ex EBV, HSV, CMV
What’s the condition
Paracortical hyperplasia
Hyperplasia:
Describe the features of Sinus histiocytosis (aka Reticular hyperplasia)
Hypertrophy/hyperplasia of lymphatic endothelial cells lining the lymphatic sinusoids
&
Increase in histocytes (macrophages in the lymph node)
Sinusoids are distended/expanded
What is a common pathological finding regarding the lymphatic sinuses in breast cancer?
Sinuses histiocytosis (reticular hyperplasia) where there’s Hypertrophy/hyperplasia of lymphatic endothelial cells lining the lymphatic sinusoids braining the breast
&
Increase in histocytes (macrophages in the lymph node)
Pre-cursor B-cell neoplasms:
Describe the etiology of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Tumor activity targets lymphoblasts (aka B-cell development)
Happens in kids under 15yrs old, peak incidence ~3yrs (higher risk in Hispanics)
Pre-cursor B-cell neoplasms:
Describe the pathogenesis of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Loss-of-function mutation of genes involved in B-cell development:
- PAX5
- E2A
- EBF
&
Translocations of (12:21) involving the ETV6 & RUNX1 genes
Pre-cursor B-cell neoplasms:
Describe the morphology of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
1) Hypocellular bone marrow packed with lymphoblasts & apoptosis inducing macrophages giving it a Starry-sky appearance
2) Tumor cells have condensed/finely stippled nuclear chromatin, small nucleoli, & a scant rim of agranular cytoplasm
1) Hypocellular bone marrow packed with lymphoblasts & apoptosis inducing macrophages giving it a Starry-sky appearance
2) Tumor cells have condensed/finely stippled nuclear chromatin, small nucleoli, & a scant rim of agranular cytoplasm
Describes the morphology of what condition?
B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Loss-of-function mutation of genes involved in B-cell development:
- PAX5
- E2A
- EBF
&
Translocations of (12:21) involving the ETV6 & RUNX1 genes
Describes the pathogenesis of what condition
B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Tumor activity targets lymphoblasts (aka B-cell development)
Happens in kids under 15yrs old, peak incidence ~3yrs (higher risk in Hispanics)
Describes the etiology of what condition?
B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Pre-cursor B-cell neoplasms:
Describe the immunotype of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
TdT +
CD19+
CD22+
CD10+
PAX5+
The following immunotype indicates what condition?
TdT +
CD19+
CD22+
CD10+
PAX5+
B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Pre-cursor B-cell neoplasms:
Describe the clinical signs of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Abrupt onset (days-weeks)
1) Hypocellular bone marrow symptoms
- Fatigue
- Anemia
- Fever
- Neutropenia
- Thrombocytopenia (bleeding)
- Higher risk of infection
2) Generalized metastasis
- Bone pain (expanding marrow)
- Generalized lymphadenopathy, hepatosplenomegaly, &
testicular enlargement
3) CNS metastasis
- Headaches, vomiting, & nerve palsies (from meningeal
spread)
Abrupt onset (days-weeks)
1) Hypocellular bone marrow symptoms
- Fatigue
- Anemia
- Fever
- Neutropenia
- Thrombocytopenia (bleeding)
- Higher risk of infection
2) Generalized metastasis
- Bone pain (expanding marrow)
- Generalized lymphadenopathy, hepatosplenomegaly, &
testicular enlargement
3) CNS metastasis
- Headaches, vomiting, & nerve palsies (from meningeal
spread)
clinical signs of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
Pre-cursor B-cell neoplasms:
Describe the signs of GOOD prognosis of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
1) Onset is between 2-10yrs old
2) Low WBC #
3) Hyper diploidy (more genetic intervention opp. for medicine)
4) Translocation at (12:21)
1) Onset is between 2-10yrs old
2) Low WBC #
3) Hyper diploidy (more genetic intervention opp. for medicine)
4) Translocation at (12:21)
Indicate a _______ prognosis for B-ALL
Good :)
Pre-cursor B-cell neoplasms:
Describe the signs of POOR prognosis of B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)
1) Onset under 2yrs old (infantile translocations involving MLL gene)
2) Presents in adolescence or adulthood
3) Peripheral blood blast levels above 100,000
1) Onset under 2yrs old (infantile translocations involving MLL gene)
2) Presents in adolescence or adulthood
3) Peripheral blood blast levels above 100,000
Indicate a _______ prognosis for B-ALL
Poor :(
Trisomy 21 (Down syndrome) has what similarity to B-ALL
People with XXX21 have a higher risk of developing acute lymphoblastic lymphoma which often present with enlarged testicles
