Pathology White cell disorders I - Zaloga Flashcards
1
Q
myeloid tissues
A
- include bone marrow and derived cells
- bone marrow is “house” for all progenitor cells
2
Q
lymphoid tissues
A
-include thymus, spleen, lymph nodes, MALT and resident cells
3
Q
where does primary hematopoiesis occur?
A
-bone marrow and thymus**
4
Q
where does secondary hematopoiesis occur?
A
-spleen, lymph nodes, tonsils, peyer’s patch
5
Q
HSC vs. multipotent progenitors
A
- HSC - pluripotent, can develop into any mature cell, self renewal, no surface markers (cannot identify), used in transplants
- multipotent progenitor - go down a cell lineage (terminal differentiated), less self renewal, higher proliferation
- differentiation driven by cytokines/growth factors
- increase division as cell matures –> change in surface markers
- unregulated clonal expansion with hematopoietic tumors
6
Q
what does G-CSF and IL-5 do?
A
- G-CSF –> stimulate granulocyte precursors
- IL-5 –> stimulate eosinophilia
7
Q
sinusoids
A
-where formed elements enter the blood from the marrow
8
Q
marrow morphology
A
- myeloid cells (granulocytes) paratrebecular
- RBCs surround Macs to get Fe
- megakaryocytes surround next to sinusoids to release platelets
leukoerythroblastosis –> immature precursors released into blood
9
Q
leukopenia
A
- low WBC count
- neutropenia most common**
- lymphopenia less common (in HIV, steroids, autoimmune, viral infections)
10
Q
proliferative disorders
A
- expansion of leukocytes
1. reactive - has inflammation/infection
2. neoplastic - no inflammation, just proliferation forming tumor
11
Q
neutropenia aka agranulocytosis
A
- risk of hematologic disease or increased risk for infection**
- see ulcerating lesions of mucous membranes from bacterial/fungal infection
- risk for deep fungal infections by candida and aspergillum
- massive organism growth, little leukocyte response
12
Q
levels of neutropenia**
A
Mild: 1.0-1.5×109 neutrophils/L
Moderate: 0.5-0.9×109 neutrophils/L
Severe: <0.5×109 neutrophils/L
13
Q
downey cells**
A
- activated lymphocytes reacting EBV, CMV**
- atypical lymphocytes
14
Q
causes of neutropenia
A
- ineffective/inadequate erythropoiesis
- suppression of HSC
- drug suppression of precursors –> drug toxicity most common cause** (chemo, alkylating agents, sulfonamides, pmenothiazines) –> high risk of infection**
- ineffective hematopoiesis from megaloblastic anemia –> apoptosis
- inherited gene defects that impair granulocyte proliferation
- increased destruction or sequestration –> from severe infection or splenomegaly**
- increased destruction of neutrophils –> hyper cellular marrow*
- agranulocytosis (from overwhelming infection) –> hypocellular marrow*
15
Q
reactive proliferations of WBC –> leukocytosis
A
- increase in WBC count
- inflammation, infection, hypoxia increase release from storage pool
- exercise and catecholamines increase demargination (break off of vessel walls)
- cortisol decreases extravasation into tissues
16
Q
neutrophilic leukocytosis causes
A
- infection, inflammation most important**
- acute infection –> increase neutrophil production via TNF from Macs (also increase other cells from bone marrow via cytokines)
17
Q
leukocytosis types**
A
- Neutrophilia: Acute bacterial infection, sterile inflammation (ex. tissue necrosis)
- Eosinophilia: Allergy, parasites, drug reaction, certain malignancies (Hodgkin)**, autoimmune disorders
- Basophilia: Rare, indicates myeloproliferative disease (ex. CML)**
- Monocytosis: Chronic infections (ex. tuberculosis)**, rickettsiosis, malaria, autoimmune disorder
- Lymphocytosis: Accompanies monocytosis, associated with chronic immune stimulation (ex, tuberculosis), viral** infections
18
Q
sepsis or sever inflammatory disorders
A
-changes in neutrophils: toxic granulations, dohle bodies** (ER in neutrophils showing overwhelming infection)
19
Q
left shift
A
- increased production of immature neutrophils (band cells) due to infection
- bone marrow working harder to release more granulocytes
20
Q
reactive vs. neoplastic leukocytosis
A
- reactive: severe infections where granulocytes mimic myeloid leukemia (leukemoid rxn)
- LAP (leukocyte alkaline phosphatase) elevated due to infection - neoplastic: acute viral infections where many lymphocytes resemble neoplastic cells
- LAP low bc there is no infection
21
Q
lymphadenitis: reactive proliferations of lymph nodes
A
- B cells: bone marrow –> primary lymphoid follicle in lymph nodes
- T cell stimulation from antigen produces secondary lymphoid follicle with germinal center where B cells create high affinity antibodies
- plasma cells release antibodies - T cells: thymus –> paracortex of lymph node
- macrophages in medulla
22
Q
acute nonspecific lymphadenitis
A
- nodes enlarged, painful, and suppurative
- draining sinuses of teeth or tonsils**
- due to systemic viral infections
- large reactive germinal centers
- histiocytes travel to where neutrophils destroyed pyogenic bacteria –> apoptosis/necrosis –> macrophages clean up debris
- lots of neutrophils, Macs, and necrosis –> not neoplastic process**
23
Q
chronic nonspecific lymphadenitis
A
- nontender, slowly enlarging nodes
- in inguinal and axillary nodes**
- follicular hyperplasia with humoral response (by any antigen or bacteria)**
- polarized germinal center: centroblasts in dark zone (develop high affinity antibodies), centrocytes in light zone**
- DCs present antigens to B cells in germinal center, macrophages phagocytose B cells that can’t make high affinity antibodies
- favors reactive hyperplasia, not neoplastic process
- paracortical hyperplasia from stimuli that trigger T cell mediated response like acute viral infection (ex. mono from EBV)** –> expanded T cell zone, less follicular hyperplasia
- sinus histiocytosis: increase cells lining sinusoids like Macs and endothelial cells –> used to drain cancers (ex. breast cancer)**
24
Q
hemophagocytic lymphohistiocytosis (HLH)
A
- aka macrophage activation syndrome** (also activate CD8 T cells)
- triggered by infection, EBV most common**
- lead to cytopenias and systemic inflammation
- phagocytize cells and suppress hematopoiesis with cytokine storm (shock like syndrome)
- familial forms and mutations –> cannot form cytotoxic granules –> febrile and hepatosplenomegaly
- may see hepatitis, DIC, multi organ failure, shock, death
25
Q
myeloid neoplasms - originate in bone marrow
A
- Acute myeloid leukemias –> myeloid progenitor cells accumulate in marrow
- Myelodysplastic syndromes –> ineffective hematopoiesis and peripheral cytopenias
- Chronic myeloproliferative disorders –> increased production of one or more terminally differentiated myeloid elements
26
Q
leukemia vs lymphoma
A
- leukemia: blood cells or bone marrow –> affect spleen or liver when entering circulation
- lymphoma: cancer in lymph nodes –> cannot enter circulation
27
Q
lymphoid neoplasms - tumors of B,T, NK origin
A
-stop normal maturation –> uncontrolled proliferation
28
Q
chromosomal mutations leading to neoplastic proliferation
A
- oncoproteins block normal maturation, activate pro-growth, and protect from apoptosis
- mutations in transcription regulators enhance self-renewal of tumor cells (MLL translocation, PML-RARA fusion gene)
- tyrosine kinase –> + RAS, PI3K/AKT, MAPK –> pro growth
- BCL2 translocation –> inhibit apoptosis
- Neoplasia from the proto-oncogenes being turned on (due to errors in antigen receptor gene) and releasing their products
- MYC (protooncogen) and BCL6 (TF for transcription repression) activated in germinal center B cell lymphomas
29
Q
lymphotrophic viruses and associated lymphomas**
A
- HTLV1 –> adult T cell leukemia/lymphoma (ATLL)
- EBV –> Burkitt lymphoma, Hodgkins lymphoma, B-cell lymphoma with T-cell immunodeficiency, NK-cell lymphoma
- HHV-8 (Kaposi sarcoma, malignant effusion B-cell lymphoma)
30
Q
agents that cause chronic inflammation –> lymphoid hyperplasia and neoplasia
A
- H. pylori –> gastric B cell lymphoma
- gluten sensitive enteropathy –> intestinal T cell lymphoma
- smoking –> AML
