Hematopoetic and Lymphoid Systems

Question 1

Causes of anemia

Answer 1

• Blood loss (hemorrhage)
• Increased red cell destruction (hemolysis)
• Decreased red cell production

Question 2

Morphology anemia

Answer 2

• Microcytic (iron deficiency, thalassemia)
• Macrocytic (folate or vitamin B12 deficiency)
• Normocytic but with abnormal shapes (hereditary spherocytosis, sickle cell disease)

Question 3

Clinical manifestations anemia

Answer 3

• 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

Question 4

Hereditary Spherocytosis

Answer 4

• 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

Question 5

Sickle Cell Anemia

Answer 5

• 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.

Question 6

Thalassemia

Answer 6

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.

Question 7

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Answer 7

X-linked disorder caused by mutations that destabilize G6PD, making red cells susceptible to oxidant damage.

Question 8

Immunohemolytic Anemia

Answer 8

• 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.

Question 9

Malaria

Answer 9

• 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)

Question 10

Hemolytic Anemia

Answer 10

Hereditary Spherocytosis
Sickle Cell Anemia
Thalassemia
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Immunohemolytic Anemia
Malaria

Question 11

Anemia of Diminished Erythropoiesis

Answer 11

Iron Deficiency Anemia
Anemia of Chronic Inflammation
Megaloblastic Anemia
Aplastic Anemia
Myelophthisic Anemia

Question 12

Iron Deficiency Anemia

Answer 12

Caused by chronic bleeding or inadequate iron intake; results in insufficient hemoglobin synthesis and hypochromic, microcytic red cells

Question 13

Anemia of Chronic Inflammation

Answer 13

Caused by inflammatory cytokines, which increase hepcidin levels and thereby sequester iron in macrophages, and also suppress erythropoietin production

Question 14

Megaloblastic Anemia

Answer 14

• 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

Question 15

Aplastic Anemia

Answer 15

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

Question 16

Myelophthisic Anemia

Answer 16

• 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

Question 17

Lymphoid Neoplasms

Answer 17

• 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

Question 18

Acute Lymphoblastic Leukemia/Lymphoma

Answer 18

• 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

Question 19

Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia

Answer 19

• 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.

Question 20

Follicular Lymphoma

Answer 20

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

Question 21

Mantle Cell Lymphoma

Answer 21

• 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

Question 22

Extranodal Marginal Zone Lymphoma

Answer 22

• 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.

Question 23

Diffuse Large B Cell Lymphoma

Answer 23

• 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

Question 24

Burkitt Lymphoma

Answer 24

• 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

Question 25

Multiple Myeloma

Answer 25

• 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)

Question 26

Hodgkin Lymphoma

Answer 26

• 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.

Question 27

Myeloid Neoplasms

Answer 27

• Myeloid tumors occur mainly in adults and fall into three major groups
  
  • AML
  • MDS
  • Myeloproliferative neoplasms

Question 28

AML

Answer 28

• 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

Question 29

MDS

Answer 29

• Myeloid tumors characterized by disordered and ineffective hematopoiesis
• Manifest with one or more cytopenias and progress in 10% to 40% of cases to AML

Question 30

Myeloproliferative neoplasms

Answer 30

• 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.