Leukocyte Disorder Flashcards
Leukocyte Disorder Type- Too Few
Leukopenia - Neutropenia (most common cause)/
Agranulocytosis (baso/eosino/neutrophils)
-Etiology -
-decreased production or activity
due to aplastic anemia or drugs,
-decreased survival due to infectious processes, immune or splenic destruction
-acquired clinical states.
Leukocyte Disorder Types- Too Many
Leukocytosis
Lymphocytosis
Lymphoid Neoplasms and leukemias (many)
Too many - Leukocytosis
Etiology - Increased cell activity Release fro bone marrow Demargination from vessel walls Reactive inflammatory states. *Cytokines stimulates release of WBCs from bone marrow. Macrophages circulate into tissue and when activated, they're stimulated to divide.
Too many - Lymphocytosis - Infectious Mono
Etiology - Epstein Barr infection of B-cells
Patho - Infected B cells secrete antibodies (heterophil antibodies diagnostic for mono - spot test_
-Antibodies produced against EBV (memory B cells for life)
-Tc and K control EBV.Tc particular to EBV called atypical lymphocytes and diagnostic of mono.
Too Many - Lymphocytosis - Infectious Mono - clinical manifestation
- Leukocytosis with atypical lymphocytes
- Lymphadenopathy
- Splenomegaly
- Infection by EBV risk for autoimmune disease and neoplasm
Too Many - Lymphoid Neoplasms & Leukemias - General info
Derived from neoplastic proliferation of B, T, or NK lymphocytes.
- most are of B cell origin
- WHO classifies on cell origin, differentiation, clinical features, and genotype.
- Myeloid Neoplasms arise from hematopoietic stem cells
- Leukemia tumors involve bone marrow.
- Clinical manifestations are similar as they can spill into each other.
Lymphoid neoplasms and leukemias - General Characteristics (know)
-Uncontrolled proliferation of a single progenitor cell (gene mutation to one cell proliferates and accumulates).
-Decreased production and function of normal hematopoietic cells.
-Acute lymphomas and leukemias-
undiff or immature cells
(blast cell from myeloid or lymphoid lines, cells not functional, differentiation blocked).
-Chronic lymphomas and leukemias-
cell differentiated, mature but do not functional normally.
Lecture info on lymphoid neo & leukemias
Leukemia
Lymphoid Neoplasms - general clinical manifestation (know)
- Spleno and Hepatomegaly & lymphadenopathy
- Lymphedema
- Constitutional symptoms (B symptoms)
- Fatigue, fever, night sweats, wt loss.
- Increased metabolic active cells and cytokine release (action of IL-1 & TNFa). - Susceptible to infection and immune disorder (no tolerance to self antigen, lymphocytes dysfunctional).
Lecture on clinical manifestation Lymphoid Neoplasms
- TNFa and IL 1 lead to systemic symptoms (B symptoms).
- When immune systems activated (B & T cells), it activates inflammatory system (IL1 an TNFa).
- Proliferation decreases production and prolix of T & B cells leading to infection susceptibility.
Luekemias - general clinical manifestation (know)
- elevated WBC 15-150K - spills into blood leading to elevated WBC
- Neutropenia (stem cell suppression)
- Anemia
- Thrombocytopenia
- Bone pain (due to marrow pressure)
- Spleno/hepatomegaly & lymphadenopathy
- B symptoms or constitutional - (fever, wt loss, night sweats, fatigue).
- Cytokines/TNF can decrease production of erythropoietin.
Lymphoid Neoplasm - Hodgkins Lymphoma
- Arises from germinal cancer B cells
- Epi - one for common in young adults, another form common >50.
- Etiology - preceding infection (mostly EBV), immunodeficiency
- Patho - Mutant B cell in single node and spreads (initial involvements typically above diaphragm).
- Spreads to spleen, liver, bone marrow.
- Extranodal involvement uncommon.
Lymphoid Neoplasm - Hodgkins Lymphoma - clinical manifestation
In addition to General manifestations:
- Reed-Sternberg giant cells (seen in background of non-neoplastic inflam. cells).
- Painless, enlarged nodes
- Staged I-IV (stage I-II 90% survival, III-IV 60-70%
Lymphoid Neoplasm - Non-Hodgkins Lymphoma
- Tumor composed of neoplastic lymphoid cells (occur 3X > Hodgkins).
- Epi - Age >50, men>women (6-8%)
- Etiology - HIV/AIDS, EBV, Hep C, immunosuppression, herbicides/chemicals
Lymphoid Neoplasm - Non-Hodgkins
- Patho - T or B cell gene mutation during develop or differentiation.
- Dx and classif. require test to determine lineage and maturity.
- Manifestations of disease dependent on which T or B cell gene affected.
- Widely disseminated by diagnosis time.
Clinical differences between hodgkin and non- (KNOW)
Kumar p 442
Hodgkin:
1. Localized to single axial group (cervical, mediastinal, para-aortic)
2. Orderly spread (contiguous)
3. Mesenteric nodes and Waldeyer ring rarely invovled.
4. Extranodal involvement uncommon
Non-Hodgkin:
1. Frequent involvement of peripheral nodes.
2. Non -contiguous spread
3. Mesenteric nodes and Waldeyer ring involvement
4. Extranodal involvement common.
Lymphoid Neoplasm - Multiple Myeloma
Etiology - gene mutation translocation of plasma B cells (myeloma plasma cells)
Epi - adults 50-60, black males
Risk factors - Farmers, cosmetologists, radiation, herpes virus, petrochemical workers.
Lymphoid Neoplasm - Multiple myeloma - Pathophys
- Myeloma plasm cells accumulate in bone marrow (characteristic).
- Fibroblasts and macrophages in marrow produce IL6, causing plasma cell proliferation.
- Lymph node involvement + extranodal sites
- Cells produce excessive # of immunoglobulin (IgG or IgA).
- It is a mutated immnunoglobulin (called Serum M protein) decreasing production of normal immunoglobulin.
Lymphoid Neoplasm - Multiple myeloma - Pathogenesis
Myeloma plasma cells secrete osteoclast-secreting factors that lead to bone destruction and reabsorption and replace normal bone marrow.
Lymphoid Neoplasm - Multiple Myeloma - clinical manifestation
In addition to general manifestations:
- Punched out bone and bone pain.
- HyperCa+ and fractures
- Increased infection
- Pancytopenia
- Blood smear - myeloma cells
- Renal insufficiency due to Bence-Jones proteins.
Leukemia - Acute Lymphoctic Leukemia (ALL)
-Etiology - genetic alteration, virus, radiation
-Epi - up to young adults, peaks age 4, older adults
-Pathogenesis - Pre B or Pre T cell mutation (80% B cell origin) Express ALL antigen
-Pre B cell involvement - Marrow overproduction and proliferation of undiff B-lymphoblasts.
Inflitrate live, spleen, lymph node.
-If Pre T cell has left to thymus, then T-lymphoblasts proliferation takes place there (do not mature and differentiate).
Leukemia - Acute Lymphocytic Leukemia (ALL) - clinical manifestations
In addition to general manifestations:
- Rapid onset of symptoms
- Blood smear - lymphoid blast cells, few mature leukocytes, anemia
- Thrombocytopenia
- Bone marrow - high number of blast cells
- Bone Pain
- Liver/spleen/lymph node enlargement
Leukemia - Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma
- Etiology - gene mutation with no link to radiation, virus, or chemicals.
- Epi - age 50-60, Western world, males
- Patho - Neoplasm of MATURE B cells.Mature B cell proliferates and accumulates but cannot differentiate into plasma cell.
Leukemia - Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma - clinical manifestations
- Develops slowly. Asymptomatic for long time.
- Blood smear - B cells in marrow. WBC 200K, small round lymphocytes easily disrupted called –Smudge cells (*characteristic!!).
- Hypogammaglobulinemia - increased risk infection
- Anemia, thrombocytopenia
- Lymphadenopathy/splenomegaly in60% of cases.
Leukemia - Acute Myelogenous Leukemia
- Etiology - toxins, chemo, radiation, chromosomal mutations, myelodysplastic syndrome.
- Epi - > age 60 (about 50%)
- Patho - abnormal proliferation of myeloid stem cell or myeloid precursor cells.
- Arrested cellular differentiation.
- Clinical manifestations - bone marrow smear >20% early myeloid cells (*characteristic!!)
- Blood smear - Increased blast or promyelocyte cells. Decreased WBC, RBC, Platelet cells.
Leukemia - Chronic Mylelogenous Leukemia
- Etiology - acquired genetic alteration (95% due to mutation of Philadelphia chromosome *characteristic!!! or BCR-ABL).
- Epi - Age 25-60, peak 40-50
- Patho - Immature granulocytes but more mature than in AML.
- Clinical Manifestation:
1. Blood smear - leukocytosis>abnormal granulocytes
2. Bone marrow - increase neoplastic granulocyte precursors
3. Splenomegaly
4. Increased hematopoieses - extra medullary hematopoesis
5. Stages - chronic/stable, accelerated, acute/blast crisis
