Pathophysiology II Exam 1 Hematopoeitic

What to look for in Acute (lymphocytic or myeloid) leukemia

(Related to suppression of elements of the bone marrow) •anemia •bleeding •fever •infection •night sweats •weight loss •paleness •lethargy •malaise

Hematopoietic

Blood forming

Many idiosyncratic cases of drug-induced neutropenia are thought to be caused by...

Immunologic mechanisms, w/ the drug or it's metabolites acting as antigens (haptens) to incite the production of antibodies reactive against the neutrophils

Lymphatic vessels functions

prevent edema by moving fluid and proteins from interstitial spaces to venous circulation; they also reabsorb fats from the small intestine.

Hematopoiesis is carried out by red bone marrow. & Bone marrow contains...

stem cells, which may develop into several different cell types during hematopoiesis.

The hematologic system functions as

an important part of the body's defenses.

Discuss the role of cytokines and colony-stimulating factors in the regulation of blood cells.

-Cytokines: short-lived mediators that stimulate the proliferation, differentiation, & functional activation of the various blood cells -Colony-stimulating factor: they have only limited capacity for self-renewal but retain the potential to differentiate into lineage-specific precursor cells; have morphological characteristics that permit them to be recognized as the first cell of a particular cell line- they have lost their ability for self-renewal but undergo cell division & differentiation, eventually giving rise to mature lymphocytes, monocytes, granulocytes, megakaryocytes, or erythrocytes

Learning Objective 3. List the three types of white blood cells and briefly describe their function.

-Granulocytes: phagocytic cells -Lymphocytes: migrate through peripheral lymphoid organs where they recognize antigen & participate in immune responses -Monocytes: travel from bone marrow to body tissues, where they differentiate into various tissue phagocytes; during inflammation, monocytes leave the blood vessel at the site of inflammation & transform into tissue macrophages that phagocytose bacteria & tissue debris; macrophages also play an important role in immune response by activating lymphocytes & by presenting antigen to T cells

Explain the difference between lymphoid and myeloid stem cells and identify the cells that arise from each.

-Lymphoid stem cells: migrate to the thymus, lymph nodes, spleen, & mucus-associated lymphoid tissues [consists of the following cells:(T cell)(NK cell)(B cell)(plasma cell)] -Myeloid stem cells: remain in the bone marrow [consists of the following cells:(granulocytes(neutrophils,basophils,eosinophils))(Monocyte/macrophage)(Megakaryocyte(platelets))(Erythrocyte(Reticulocyte))]

Learning Objective 4. List the three subtypes of granulocytes and briefly describe their role & their % composition of total WBCs

-Neutrophils: primary antigen-fighting cells (60-65% total WBCs) (Nuclei divided into 3-5 lobes) -Eosinophils: help control allergic reactions & fight parasites (1-3# of total WBCs) (Many bright red-stained granules) -Basophils: secrete heparin, histamine, & other inflammatory mediators (0.3-0.5% of total WBCs) (Dark blue-staining granules)

Explain the meaning of pluripotent stem cell and colony-forming unit (CFU).

-Pluripotent stem cells: give rise to 2 types of multi potent stem cells (the hematopoietic (common myeloid) stem cells(remain in bone marrow) & the lymphopoietic (common lymphoid) stem cells (migrate to the lymphoid tissues)) -Colony-forming unit (CFU): several levels of differentiation lead to the development of committed unipotential cells, which are the progenitors for each of the blood cell types

Learning Objective 5. Describe the role of the lymphoid tissues. (Using examples, explain the difference between central and peripheral lymph organs)

-The body's lymphatic system consists of the lymphatic vessels, lymphoid tissue & lymph nodes, thymus, & spleen. -T lymphocytes migrate to peripheral lymphoid structures to complete the differentiation process: they leave bone marrow as precursor T lymphocytes & travel to the thymus (& differentiate into CD4 helper T cells & CD8 cytotoxic T cells), afterwards move to lymph nodes(& undergo further proliferation) -B cells differentiate into plasma cells & then move to the lymph nodes, where they can cont. to proliferate & produce antibodies

Hodgkin lymphoma (HL)

...

complications of acute leukemia and its treatment: *blast crisis*

...

complications of acute leukemia and its treatment: *tumor lysis syndrome*

...

non-Hodgkin lymphoma (NHL)

...

Mild Neutropenia

1000 cells/mcgL

Moderate Neutropenia

500-1000 cells/mcgL

Severe Neutropenia

<500 cells/mcgL

Acute lymphocytic leukemia

Abnormal growth of lymphocytic precursor (lymphoblasts)

Aplastic anemia

All of the myeloid stem cells are affected, resulting in anemia, thrombocytopenia, & agranulocytosis

Erythrocytes (red blood cells [RBCs])

Are formed in the bone marrow and contain hemoglobin.

Identify the two types of cells that arise from pluripotent stem cells.

Common lymphoid stem cells & common myeloid stem cells

Leukopenia

Decrease in the absolute number of leukocytes in the blood

Granulocytopenia/Agranulocytosis

Denotes a virtual absence of neutrophils

Idiosyncratic

Describes drug reactions that are from different from the effects observed in most persons and that cannot be explained in terms of allergy

Trace the development of the different blood cells from their origin in the pluripotent bone marrow stem cell (to lymphoid stem cell) to their circulation in the bloodstream

Pluripotent stem cell>lymphoid stem cell> 1.NK progenitor>NK cell 2.T cell progenitor>*thymus*>T cell 3.B cell progenitor>B cell>plasma cell

Trace the development of the different blood cells from their origin in the pluripotent bone marrow stem cell (to myeloid stem cell) to their circulation in the bloodstream

Pluripotent stem cell>myeloid stem cell> 1.Monocyte>Monoblast>Monocyte 2.Granulocyte> Eospinophil, Neutrophil, or Basophil 3.Megakaryocyte>Megakaryocyte>platelets 4.Erythrocyte>Reticulocyte>Erythrocyte

Identify the three types of white blood cells that are the result of hemopoiesis

Pluripotent stem cells, multi potent stem cells, & committed progenitor cells

Acute myelogenous leukemia

Rapid accumulation of myeloid precursors (myeloblasts)

Pancytopenia

Reduced number of all cellular elements of the blood

Neutropenia

Refers specifically to an abnormally low # of neutrophils & is commonly defined as a circulating neutrophil count of <1500 cells/mcgL

Leukemia

Refers to a group of malignant disorders characterized by abnormal proliferation & maturation of lymphocytes & nonlymphocytic cells, leading to the suppression of normal cells •it can be classified as acute or chronic, w/ sub classifications of lymphocytic or myelogenous

Learning Objective 9. Define infectious mononucleosis and describe the pathogenesis, clinical manifestations, and treatment. Explain the cause of infectious mononucleosis and cite its prevalence. Describe the pathology, clinical course, typical lab results, and treatment for infectious mononucleosis. (Refer to Figure 11-5.)

Viral illness caused by the Epstein-Barr virus, a B-lymphotropic herpes virus. ● Most cases spread by the oropharyngeal route, but transmission by blood transfusion or during cardiac surgery is also possible. ● The virus invades the B cells of the oropharyngeal lymphoid tissues and then replicates. ● Dying B cells release the virus into the blood, causing fever and other symptoms. During this period, antiviral antibodies appear and the virus disappears from the blood, lodging mainly in the parotid gland.

Chronic lymphocytic leukemia shows

a proliferation of small abnormal mature B cells and decreased antibody response.

In stage I of Hodgkin's disease, symptoms include

a single enlarged lymph node (usually), unexplained fever, night sweats, malaise, and generalized pruritus.

The spleen

destroys bacteria, filters blood, serves as a blood reservoir, forms lymphocytes and monocytes, and traps formed particles.

complications of acute leukemia and its treatment: *leukostasis*

is a condition in which the circulating blast count is markedly elevated (usually 100,000 cells/mcgL). The high number of circulating leukemic blasts increases blood viscosity and predisposes to the development of leukoblastic emboli with obstruction of small blood vessels in the pulmonary and cerebral circulations. •Occlusion of the pul- monary vessels leads to vessel rupture and infiltration of lung tissue, resulting in sudden shortness of breath and progressive dyspnea. Cerebral leukostasis leads to diffuse headache and lethargy, which can progress to confusion and coma. •Tx: Once identified, leukostasis requires immediate and effective treatment to lower the blast count rapidly. Initial treatment uses apheresis to remove excess blast cells, followed by chemotherapy to stop leukemic cell production in the bone marrow

The initial phase of chemotherapy for acute lymphocytic leukemia, called the induction phase,

is designed to put the client into remission by giving high doses of drugs and administering doses closer together than once each month.

complications of acute leukemia and its treatment: *hyperuricemia*

occurs as the result of increased proliferation or increased breakdown of purine nucleotides (i.e., one of the components of nucleic acids) secondary to the leukemic cell death that results from chemotherapy. may increase before and during treatment. •Tx: Prophylactic therapy with allopurinol, a drug that inhibits uric acid synthesis, is routinely administered to prevent renal complications secondary to uric acid crystallization in the urine filtrate.

Uncontrolled proliferation of granulocytes

occurs in myelogenous leukemia

Learning Objective 7. Cite two general causes of neutropenia. Identify causes of neutropenia. (Refer to Chart 11-1.)Learning Objective 8. Describe the mechanism of symptom production in neutropenia. For each cause, list the effect on neutrophils that results. Describe the clinical manifestations associated with neutropenia. .

•Congenital -alloimmune neonatal neutropenia (transfer of maternal antibodies) - cyclic neutropenia (autosomal disorder w/ variable expression that in infancy & persists for decades)(develops every 21 days & lasts ~2 to 3 days) - Kostmann syndrome (severe congenital neutropenia) (rare inherited form)(occurs sporadically or as an autosomal recessive disorder, causing severe neutropenia while preserving the erythroid & Megakaryocyte cell lineages that result in RBC & platelet production) •Acquired -Autoimmune >primary (rare, usually occurs in kids & runs a benign course)(May cause increased & premature destruction of neutrophils) -secondary >systemic lupus erythematosus >Felty syndrome in RA -infection related >many types of infectious agents, but most commonly viruses (mechanisms include increased consumption of neutrophils, production of autoantibodies, direct infiltration of hematopoietic cells, bone marrow suppression) -drug related >immune-mediated reactions in which drugs act as haptens (penicillin, propylrhiouracil, aminopyine) >accelerated apoptosis (clozapine [antipsychotic agent) >cancer chemotherapeutic drugs (bone marrow stem cell depression w/ decreased production of all blood cell types)(cause predictable dose-dependent suppression of bone marrow function) -radiation therapy to bone marrow -hematologist malignancies (may suppress the function of neutrophil precursors)

Leukemia: how it happens

•Hematopoietic cells (immature blood cells) undergo an abnormal transformation, giving rise to leukemic cells. •Leukemic a multiply & accumulate, crowding out other cell types •Crowding prevents production of red & white blood cells & platelets, leading to pancytopenia

List the blood cells that arise from each of the two types of lymphoid tissue.

•Lymph Nodes: cortex contains well-defined *B cell* & *T cell* domains. --superficial outer cortex: aggregates of cells called "follicles">> are the B cells zones of the lymph nodes >>2 types: immunologically inactive follicles (primary follicles) & active follicles that contain germinal centers (secondary follicles): these contain large lymphocytes (centroblasts) & small lymphocytes w/ cleaved nuclei (centrocytes) --mantle zone: small layer of B cells surrounding the germinal centers --paracortex: region that contains most of the T cells in the lymph nodes •alimentary canal, resp. passages, & GU systems are guarded by accumulations of lymphoid tissue that are not enclosed in a capsule: called diffuse lymphoid tissue or mucosa-associated lymphoid tissue (MALT) b/c of its association w/ mucous membranes. >> lymphocytes are found in the subepithelium of these tissues.

Hematopoiesis (occurs in) (& the process)

•Occurs in the spleen •is the process by which red blood cells, white blood cells, and platelets are produced.

Lymph nodes

•are tissues that filter out bacteria and other foreign cells and are grouped by region. •are grouped by region: cervicofacial, supraclavicular, axillary, epitrochlear, inguinal, and femoral.