WBCs

Hematopoetic stem cell is located in the BM and is CD34+ o Can become myeloid or lymphoid Normal WBC count is 5-10K o Low WBC is leukopenia o High WBC is leukocytosis o Either a leukopenia or leukocytosis is normally due to one specific cell type Ex: neutropenia Seen w/ drug toxicity (chemo therapy) and sever infection o Treat the neutropenia from chemo w/ GM-CSF or G-CSF o Severe infection will cause the neutrophils to move out of the blood and into the tissue Lymphopenia (low lymphocytes) Immunodeficiency high cortisol state o induce apoptosis in lymphocytes o cushing syndrome autoimmune destruction o lupus o abs against any of the cells circulating in the bood whole body radiation o most sensitive cell is the lymphocytes o Lymphocytes would be one of the first cells damaged by the radiation Neutrophilic leukocytosis (increased amount) Bacterial infection and Tissue necrosis o Two driving forces for acute inflammation o BM will release cells that are slightly immature Will get a left-shift Cells are characterized by decreased Fc receptors (CD16) o Help cells recognize IgG to help opsonize High cortisol state o This will release the marginating pool (found on the vasculature of the pulmonary endothelium) Cortisol will disrupt the adhesion ability Causing the marginating pool to be released

Monocytosis: o Seen in chronic inflammatory states o Malignancy Eosinophilia o Allergic rxns o Parasitic infection o Hodgkin lymphoma Subset of pts will have increased amount associated w/ the tumor and circulating around in the blood Mechanism is due to an increase in IL-5 production Basophilia o Only seen in CML Lymphocytic leukocytosis o High white count do to lymphocytes o Seen w/ viral infections CD8 cells fuck shit up o Bordetella pertussis One exception in bacteria that causes leukocytosis w/ lymphocytes Secretes lymphocytosis promoting factor Blocks lymphocytes from leaving Blood and entering the lymph node Infectious mononucleosis o EBV infection results in lymphocytic leukocytosis comprised of reactive CD8 T-cells (downey cells) CMV is a less common cause Transmitted by saliva, and classically affects teens 3 tissues will be affected: Oropharynx sore throat Liver hepatitis B-cells latent infection CD8 T-cell response due to expression of viral proteins on MHC-I Generalized lymphadenopathy in the paracortex Splenomegaly (periarterial lymphatic sheath) o Expansion of the T-cell area is the PALS High white count w/ atypical lymphocytes o CD8 T-cells Nucleus is bigger than adjacent RBCs Contains abundant blue cytoplasm (not typical of lymphocyte) Cell looks like a monocyte

Screen for mono w/ a monospot test Defects IgM heterophile antibodies

o o o Complications: Increased risk of splenic rupture Rash if exposed to penicillin Dormancy of virus in B-cells o Increased risk of infection again o Increased risk of lymphoma Esp if immunodeficiency develops

Bind RBCs from another animal (IgM anti-sheep RBC, or horse RBC) Usually positive 1 week after infection Negative if tested too early or if its due to CMV Definitive dx is made by testing for EBV viral capsid antigen

Acute leukemia o Disruption in the ability of the cells to mature o Myeloid progenitor or lymphoid progenitor loss the ability to mature Causing the progenitor cells to increase in number Neoplastic proliferation of blast cells Blasts normally present in BM at 1-2%, in acute leukemia the blasts are greater than 20% of the BM o This will crowd-out normal hematopoiesis resulting in acute presentation w/ anemia, thrombocytopenia, or neutropenia The blasts enter into the blood and result in a high WBC count o The blasts are large, immature cells, often w/ punched out nucleoli on blood smear Also doesnt have much cytoplasm o Wont be able to tell if the blasts are of the myeloid or lymphoid lineage

AML = accumulation of the myeloid blast cells o Myeloperoxidase positive (MPO) Can crystallize into auer rods Can detect them chemically o Most commonly seen in older adults Aged 50-60 o Subclassed in 3 ways Cytogenetic abnormalities Lineage of myeloblasts Erythroblastic AML, myeloblastic AML, monoblastic AML, megakaryoblastic AML Surface markers o Acute promyelocytic leukemia T(15;17) RAR (retinoic acid receptor) disrupted Disrupts ability of cells to mature accumulation of promyelocytes

Promyelocytes contain auer rods o Risk of DIC via auer rod activation of coag cascade Rx: give pt ATRA (all trans retinoic acid) o Derivative of VitA that will cause the blast cells to mature into neutrophils by binding to RAR o Acute monocytic leukemia Proliferation of monoblasts Lacks MPO Blasts characteristically infiltrate the gums Pt will present w/ infiltrates in the gums o Acute megakaryoblastic leukemia Proliferation of megakaryoblasts Lack MPO Associated w/ down syndrome before the age of 5 o AML can arise from a pre-existing dysplasia Due to prior exposure to alkylating agents or radiotherapy Pts will develop a myelodysplastic syndrome o Cytopenias w/ hypercellular BM Cytopenia due to abnormal cells not getting out into the BM o Abnormal maturation w/ increased blasts (<20%) In BM o Most pts die from infection or bleeding (due to cytopenia) o Progression to acute leukemia (>20% blasts) AML arising in the background of myelodysplasia ALL = accumulation of the lymphoid blast cells o TDt positive DNA pol used to make the B/T cell receptor in the nucleus Gets lost in mature lymphocytes Arises in children and may be associated w/ down syndrome (after the age of 5) o Subdivided into B-ALL and T-ALL B-ALL is the most common type Expresses CD10, CD19, CD20 on its surface Excellent response to chemo o Needs to be prophylaxed into the CNS and scrotum (does not cross BBB or BTB) Prognosis is based on cytogenetic abnormalities o T(12:21) has a good prognosis Most commonly seen in kids o T(9:22) has a poor prognosis (ph+ ALL) Most commonly seen in adults T-ALL (acute lymphoblastic lymphoma) Lymphblasts that express markers ranging from CD2-CD8 o Blast do not express CD10 Presents as a thymic mass in a teenager