Hematopoetic and Lymphoid Systems Flashcards
Causes of anemia
- Blood loss (hemorrhage)
- Increased red cell destruction (hemolysis)
- Decreased red cell production
Morphology anemia
- Microcytic (iron deficiency, thalassemia)
- Macrocytic (folate or vitamin B12 deficiency)
- Normocytic but with abnormal shapes (hereditary spherocytosis, sickle cell disease)
Clinical manifestations anemia
- Acute: shortness of breath, organ failure, shock
- Chronic
- Pallor, fatigue, lassitude
- With hemolysis: jaundice and gallstones
- With ineffective erythropoiesis: iron overload, heart and endocrine failure
- If severe and congenital growth retardation, bone deformities due to reactive marrow hyperplasia
Hereditary Spherocytosis
- Autosomal dominant disorder caused by mutations that affect the red cell membrane skeleton, leading to loss of membrane and eventual conversion of red cells to spherocytes, which are phagocytosed and removed in the spleen.
- Manifested by anemia, splenomegaly
Sickle Cell Anemia
- Autosomal recessive disorder resulting from a mutation in B-globin that causes deoxygenated hemoglobin to self-associate into long polymers that distort the red cell.
- Blockage of vessels by sickled cells cause pain crises and tissue infarction, particularly of the marrow and spleen.
- Red cell membrane damage caused by repeated bouts of sickling results in a moderate to severe hemolytic anemia.
- Patients are at high risk for bacterial infections and stroke.
Thalassemia
Autosomal codominant disorders caused by mutations in a- or B-globin that reduce hemoglobin synthesis, resulting in a microcytic, hypochromic anemia. In B-thalassemia, unpaired a-globin chains form aggregates that damage red cell precursors and further impair erythropoiesis.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
X-linked disorder caused by mutations that destabilize G6PD, making red cells susceptible to oxidant damage.
Immunohemolytic Anemia
- Caused by antibodies against either normal red cell constituents or antigens modified by haptens (such as drugs).
- Antibody binding results in either red cell opsonization and extravascular hemolysis or (uncommonly) complement fixation and intravascular hemolysis.
Malaria
- Intracellular red cell parasite that causes chronic hemolysis of variable severity.
- Falciparum malaria may be fatal because of the propensity of infected red cells to adhere to small vessels in the brain (cerebral malaria)
Hemolytic Anemia
Hereditary Spherocytosis
Sickle Cell Anemia
Thalassemia
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Immunohemolytic Anemia
Malaria
Anemia of Diminished Erythropoiesis
Iron Deficiency Anemia
Anemia of Chronic Inflammation
Megaloblastic Anemia
Aplastic Anemia
Myelophthisic Anemia
Iron Deficiency Anemia
Caused by chronic bleeding or inadequate iron intake; results in insufficient hemoglobin synthesis and hypochromic, microcytic red cells
Anemia of Chronic Inflammation
Caused by inflammatory cytokines, which increase hepcidin levels and thereby sequester iron in macrophages, and also suppress erythropoietin production
Megaloblastic Anemia
- Caused by deficiencies of folate or vitamin B12 that lead to inadequate synthesis of thymidine and defective DNA replication
- Results in enlarged abnormal hematopoietic precursors (megaloblasts), ineffective hematopoiesis, macrocytic anemia, and (in most cases) pancytopenia
Aplastic Anemia
Caused by bone marrow failure (hypocellularity) resulting from diverse causes, including exposures to toxins and radiation, idiosyncratic reactions to drugs and viruses, and inherited defects in telomerase and DNA repair
Myelophthisic Anemia
- Caused by replacement of the bone marrow by infiltrative processes such as metastatic carcinoma and granulomatous disease
- Leads to the appearance of early erythroid and granulocytic precursors (leukoerythroblastosis) and teardrop-shaped red cells in the peripheral blood
Lymphoid Neoplasms
- Cassification is based on cell of origin and stage of differentiation
- Most common types in children are ALLs/lymphoblastic lymphomas derived from precursor B and T cells
- Most common types in adults are non-Hodgkin lymphomas derived from germinal center B cells
Acute Lymphoblastic Leukemia/Lymphoma
Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia
Follicular Lymphoma
Mantle Cell Lymphoma
Extranodal Marginal Zone Lymphoma
Diffuse Large B Cell Lymphoma
Burkitt Lymphoma
Multiple Myeloma
Hodgkin Lymphoma
Acute Lymphoblastic Leukemia/Lymphoma
- Highly agressive tumors that manifest with signs and symptoms of bone marrow failrue, or as rapidly growing masses
- Tumor cells contain genetic lesions that block differentiation, leading to the accumulation of immature, nonfunctional blasts
Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia
- Mature B cell tumor that manifests with bone marrow and lymph node involvement
- Indolent course, commonly associated with immune abnormalities, including an increased susceptibility to infection and autoimmune disorders.
Follicular Lymphoma
Tumor cells recapitulate the growth pattern of normal germinal center B cells; most cases are associated with (14;18) translocation that results in the overexpression of BCL12
Mantle Cell Lymphoma
- Mature B cell tumor that usually manifests with advanced disease involving lymph nodes, bone marrow, and extranodal sites such as the gut
- Associated with an (11;18) translocation that results in overexpression of cyclin D1, a regulator of cell cycle progression
Extranodal Marginal Zone Lymphoma
- Mature B cell tumor arising at textranodal sites involved by chronic inflammation resulting from autoimmunity or infection (e.g. H. pylori)
- Remains localized for long periods and may regress if the inflammatory stimulus is removed.
Diffuse Large B Cell Lymphoma
- Heterogenous group of mature B cell tumors that shares large cell morphology and aggressive clinical behavior and is the most common type of lymphoma
- Rearrangements of mutations of BCL6 gene are recognized associations; one third carry a (14;18) translocation involving BCL2
Burkitt Lymphoma
- Very aggressive mature B tumor that usually arises at extranodal sites
- Nearly always associated with translocations involving the MYC protooncogene
- Tumor cells often are latently infected by EBV
Multiple Myeloma
- Plasma cell tumor often manifesting with multiple lytic bone lesions associated with pathologic fractures and hypercalcemia.
- Neoplastic plasma cells suppress normal humoral immunity and secrete partial immunoglobulins that are nephrotoxic (Bence Jones proteins)
Hodgkin Lymphoma
- Unusual B cell tumor consisting mostly of reactive lymphocytes, macrophages, and stromal cells
- Malignant RS cells make up a minor part of the tumor mass.
Myeloid Neoplasms
- Myeloid tumors occur mainly in adults and fall into three major groups
- AML
- MDS
- Myeloproliferative neoplasms
AML
- Aggressive tumors comprised of immature myeloid lineage blasts, which replace the marrow and suppress normal hematopoiesis
- Associated with diverse acquired mutations that lead to expression of abnormal transcription factors, which interfere with myeloid differentiation
MDS
- Myeloid tumors characterized by disordered and ineffective hematopoiesis
- Manifest with one or more cytopenias and progress in 10% to 40% of cases to AML
Myeloproliferative neoplasms
- Myeloid tumors in which production of formed myeloid elements is initially increased, leading to high blood counts and extramedullary hematopoiesis
- Commonly associated with acquired mutations that lead to signals from normal growth factors. The most common pathogenic kinases are BCR-ABL (associated with CML) and mutated JAK2 (associated with polycythemia vera and primary myelofibrosis).
- All can transform to acute leukemia and to a spent phase of marrow fibrosis associated with anemia, thrombocytopenia, and splenomegaly.
