GI: WBC Disorders Flashcards
1
Q
- Absolute Leukocyte count usually >25,000 to 30,000 cells/mm3
- May involve neutrophils, Lymphocytes, or Eosinophils
- Normal Bone marrow response to Cytokines released by cells to infection or trauma
- Normal albeit exaggerated response to an infection
A
Leukemoid Reaction
2
Q
- Presence of Immature bone marrow WBCs and Nucleated RBCs in Peripheral blood ‘Peripheralization’ of the Bone marrow, irrespective of Total Leukocyte count
- Peripheral blood findings
- Myeloblasts, Progranulocytes, and other Leukocyte precursors
- Nucleated RBCs and Teardrop RBCs (if fibrosis is present)
A
Leukoerythroblastosis
3
Q
- A low WBC count (< 5K)
- A/w advanced HIV
- Following therapy w/ Glucocorticoids or Cytotoxic drugs
- Autoimmune disorders
- Malnutrition
- Acute Viral Infections –> Type I interferons –> T lymphocytes activation –> sequestration of activated T cells in Lymph nodes and increased adherence to Endothelial cells
A
Leukopenia
4
Q
- A high WBC count (> 10K)
- Increased Production in the Marrow
- Chronic Infection or Inflammation
- Paraneoplastic
- Myeloproliferative disorders
- Increased Release from Marrow
- Endotoxemia, Infection, Hypoxia
- Decreased Margination
- Exercise, Catecholamines
- Decreased Extravasation into Tissues
- Glococorticoids
A
Leukocytosis
5
Q
- Decreased number of circulating neutrophils <1500 cells/mm3 (Serious if <500 cells/mm3)
- Aplastic anemia
- Immune destruction – SLE and Paroxysmal nocturnal Hemoglobinuria
- Septic shock
- Ticks, Viral, Bacterial, Fungal, XRT
- Drug toxicity (Chemo w/ alkylating agents) - Dmg to stem cells results in decreased production of WBCs, especially neutrophils, anti-Metabolites for Chemo Tx.
- Severe Infection (gram-negative sepsis) – increased movement of neutrophils into tissues results in decreased circulating neutrophils
- As a Tx: GM-CSF or G-CSF may be used to Boost Granulocyte production, thereby decreasing risk of infection in Neutrophenic
A
Neutropenia
(Agranulocytosis)
6
Q
- Decreased number of circulating lymphocytes
- Immunodeficiency (DiGeorge syndrome or HIV)
- High cortisol state (exogenous corticosteroids or Cushing syndrome) –> increased Cortisol –> Apoptosis
- Autoimmune destruction (SLE)
- Whole body radiation – Lymphocytes are highly sensitive to XRT – Lymphopenia is the earliest change to emerge after Whole Body XRT
A
Lymphopenia
7
Q
- Increased circulating Neutrophils >7500 cells/mm3
- Bacterial infection or Tissue necrosis – induces release of Marginated pool and Bone marrow neutrophils, including immature forms (left shift)
- Immature cells are characterized by decreased Fc receptors (CD16)
- High cortisol state – impaires leukocyte adhesion, leading to release of Marginated pool of Neutrophils
- Chronic Infections and Chronic Inflammation (Lung abcesses) –> expansion of Myeloid precursor pool in Bone marrow
A
Neutrophilic Leukocytosis
8
Q
- Increased circulating monocytes >800 cells/mm3
- Chronic inflammatory states (autoimmune (RA) and infectious (TB, Subacute infective endocarditis, Cirrhosis))
- Malignancy (carcinomas and lymphomas)
A
Monocytosis
9
Q
- Hypercortisolism (Cushing syndrome, Coricosteroids)
- Corticosteroids sequester Eosinophils in Lymph noes and Trigger apoptosis
A
Eosinopenia
10
Q
- Increased circulating eosinophils > 400 cells/mm3
- Allergic reactions (Type I Hypersensitivity – Mast cells)
- No sequestering of Eosinophils in Lymph nodes
- Parasitic infctions (Protozoa, Helminths)
- Polyarteritis nodosa, Churg-Strauss syndrome
- Job syndrome
- Addison disease (Cortisol deficiency)
- Hodgkin lymphoma (Tumor –> increased IL-5 production)
- Driven by increased Eosinophil chemotactic factor
A
Eosinohilia
11
Q
- Increased ciruclating basophils >110 cells/mm3
- Classically seen in Chronic Myeloid Leukemia (CML)
- Chronic myeloproliferative disorders (Polycythemia vera)
A
Basophilia
12
Q
- Increased circulating lymphocytes >5000 cells/mm3 in Adults and >8000 cells/mm3 in Children
- Viral infections – T lymphocytes undergo Hyperplasia in response to virally infected cells, Mononucleosis and Cytomegalovirus (CMV)
- Bordetella pertussis infection – Bacteria produce lymphocytosis – promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node (Whooping cough) and Tuberculosis
- Drugs – Phenytoin and Tetracycline
- “Stuck in the blood” –> Increased [WBC]
A
Lymphocytic Leukocytosis
13
Q
- EBV infection that results in a Lymphocytic leukocytosis –> Increased [WBC]
- EBV is transmitted by Saliva “Kissing Disease” classically affects teenagers (15 – 24 y.o.), replicates in the epithelial cells in the Oropharynx
- Comprised of reactive CD8+ T cells –> MHC class I response
- CD8+ T cell response –> Generalized Lymphadenopathy (LAD) due to T-cell hyperplasia in Lymph node Paracortex
- A/w Splenomegaly due to T-cell Hyperplasia in the Periarterial lymphatic Sheath (PALS): White Pulp –> B-cells and T-cells
- High WBC count w/ Atypical Lumphocytes (Reactive CD8+ T cells) in the blood –> Dx w/ Heterophile Ab test (Monospot test)
- CVM is a less common cause
- EBV infects: Oropharynx –> Pharyngitis, Liver –> Hepatitis w/ Hepatomegaly and Elevated Liver enzymes, B-cells
A
Infectious Mononucleosis
14
Q
- Detects IgM antibodies that cross-react w/ IgM Ab against Horse, Sheep, or Bovine RBCs (Heterophile Ab)
- Usually turns Positive w/in 1 week after Infection
- Negative Test suggests CMV as a possible cause or Test done too early
- Definitive diagnosis is made by Serologic testing for the EBV viral capsis antigen
A
Monospot Test for Infectious Mononucleosis (IM)
15
Q
- Increased risk of Splenic Rupture due to Splenomegaly –> Pts. are generally advised to avoid contact sports for One month – One year
- Rash if exposed to Ampicillin (PCN)
- Dormancy of Virus in B cells leads to Increased risk for both Recurrenc and B-cell Lymphoma, especially if Immunodeficiency (HIV) develops
A
Complications of Infectious Mononucleosis (IM)
16
Q
- Absolute lymphocyte count <1500 cells/mm3 in Adults and <3000 cells/mm3 in Children
- HIV,
DiGeorge syndrome (T-cell deficiency),
SCID (B- and T-cell def.),
Bruton agammaglobulinemia (B-cell def.),
Immune destruction (SLE) - Drugs
- XRT
A
Lymphopenia
17
Q
- Neoplastic proliferation of Blasts – Accumulation of
> 20% Blasts in the Bone Marrow - Increased Blasts “crowd-out” Normal Hematopoiesis
–> resuting in “Acute” presentation w/ Anemia (Fatigue), Thrombocytopenia (Bleeding due to loss of Platelets), or Neutropenia (Infection) - Blasts enter Blood stream –> increased [WBC] count
- Blasts are Large, Immature cells, often w/ Punched out Nucleoli
- Acute Leukemia is Subdivided: AML and ALL based on Blast Phenotype
A
Acute Leukemia Basics
18
Q
Age Ranges for Common Leukemias
A
- More common in Adults than in Children
- Newborn to 14 years old
- ALL is most common
- ALL is most common overall cancer in Children
- 40 – 60 y.o.
- AML – Acute Myeloblastic Leukemia
- CML – Chronic Myelogenous Leukemia
- > 60 y.o.
- CLL – Chronic Lymphocytic Leukemia
- CML – Chronic Myelogenous Leukemia
19
Q
- Neoplastic accumulation of Lymphoblasts (>20%) in Bone Marrow
- 3x White : Blacks
- t(9;22) BCR-ABL - Tyrosine kinase –> Tx: Gleevec a Tyrosine kinase inhibitor
- t(4,11) MLL gene on Chrom. 11q23
- t(8;14)
- CNS manifistations: Headache, Vomiting, Nerve palsies resulting from Meningeal spread - Neoplastic infiltration
- Lymphoblasts are characterized by Positive Nuclear staining for TdT (DNA polymerase)
- TdT is absent in Myeloid blasts and Mature Lymphocytes
- A/w Children, w/ Down Syndrome (> 5 y.o.)
- Subclassified into B-ALL and T-ALL based on Surface Markers
A
Acute Lymphoblastic Leukemia (ALL)
20
Q
- Lymphoblasts (TdT+) that express CD10, CD19, and CD20
- Loss of Function Mutations: PAX5, E2A, and EBF
- Excellent response to Chemo
- Mass in the Skin or a Bone
- Requires prophylaxis to Scrotom and CSF
- t(12;21) –> 25% have ETV6 and RUNX1 - Marrow replacement and Pancytopenia, Good prognosis – more commonly seen in Children “Childhood Acute Leukemia”
- t(9;22) –> Poor prognosis – more commonly seen in Adults (Phil+ALL)
A
B cell Acute Lymphoblastic Leukemia (B-ALL)
21
Q
- Lymphoblasts (TdT+) that express markers from CD2 to CD8, but NO CD10
- 70% have NOTCH1 - T cell development
- Typically evolve to Leukemic picture
- Usually presents in Teenagers as a Mediastinal (Thymic) mass (“Adolescent Males w/ Thympic Lymphomas”)
- Called Acute Lymphoblastic Lymphoma because the Malignant cells form a Mass
A
T cell Acute Lymphoblastic Leukemia (T-ALL)
22
Q
- Neoplastic accumulation of Immature Myeloid cells (>20%) in the Bone marrow
- Positive Cytoplasmic staining for Myeloperoxidase (MPO)
- Crystal aggregates of MPO may be seen as Auer Rods
- Older adults (Average age is 50 – 60 y.o.)
- Subclassified based on Cytogenic abnormalities, Lineage of Immature myeloid cells, and Surface markes
- Treatment-related AML a/w which prior therapies
- Aklylating agents
- Topoisomerase II inhibitors
- XRT
A
Acute Myeloid Leukemia (AML)
23
Q
- t(15;17) – translocation of the Chimeric protein w/ Retinoic acid receptor (RARα) fused to Promyelocytic leukemia protein (PML) –> Chrom 17 to Chrom 15; RAR disruption blocks maturation/differentiation on myeloid cells at the Promyelocytes (blasts) stage
- -> Promyelocytes and Myeloblasts accumulate
- Abnormal promyelocytes contain numerous Primary granules that increase risk for DIC
- Tx: all-trans-retinoic acid (ATRA) (Vit. A der.)
- -> binds the altered receptor and causes the blasts to mature and differentiate –> and die
A
Acute Promyelocytic Leukemia (APL)(Subclass of AML)
24
Q
- Proliferation of monoblasts; usually lack MPO
- Blasts characteristically Infiltrate the Skin and Gums (Gingival infiltrations)
A
Acute Monocytic Leukemia (Subclass of AML)
25
Q
- Proliferation of megakaryoblasts; usually lack MPO
- A/w Down Syndrome (< 5 y.o.)
A
Acute Megakaryoblastic Leukemia