The Hematopoietic and
Lymphoid Systems
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Hematopoiesis
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Overview of Major Diseases
• Anemia
• Leukemia
• Lymphoma
• Bleeding disorders
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Hematopoietic System
• Erythrocytes ideally suited for primary function: transport of oxygen
from lungs into peripheral tissues
• Hemoglobin: complex molecule consisting of four heme groups &
four globins
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Anemia
• Reduction of hemoglobin in blood to below normal levels
• In practice, this means <13 g/dL in males & <11.5 g/dL in females
• May be associated with:
• Appearance of abnormal hemoglobin
• Reduced number of red blood cells
• Structural abnormalities of red blood cells
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Anemia: Etiology & Pathogenesis
• Anemia may be a consequence of:
• Decreased hematopoiesis
• Abnormal hematopoiesis
• Increased loss or destruction of red blood cells
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Decreased Hematopoiesis
• Bone marrow failure
• Aplastic anemia
• Deficiencies of nutrients
• Deficiency of vitamin B12 & folic acid (megaloblastic anemia)
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Abnormal Hematopoiesis
• Usually a consequence of genetic abnormalities
• Sickle cell anemia
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Increased Loss & Destruction of Red
Blood Cells
• Bleeding
• Intrasplenic sequestration
• Immune hemolysis
• Infections (malaria)
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Morphology of Anemias
• Normocytic, normochromic anemia
• “Dilutional anemia”
• Microcytic, hypochromic anemia
• Iron deficiency
• Macrocytic, normochromic anemia
• Deficiency of vitamin B12 and/or folic acid
• Anemias characterized by abnormal red blood shapes
• Elliptocytosis, spherocytosis, sickle cell
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Morphology of Anemias (Cont’d)
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Aplastic Anemia
• Idiopathic, secondary
• Bone marrow depleted of hematopoietic cells; consists only of
fibroblasts, fat cells, scattered lymphocytes
• Anemia, leukopenia, thrombocytopenia
• Uncontrollable infections, bleeding tendency, chronic fatigue,
sleepiness, weakness
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Iron Deficiency Anemia
• Most common form of anemia
• Hypochromic, microcytic anemia
• Etiology:
• Increased loss of iron (e.g., chronic bleeding)
• Inadequate iron intake or absorption
• Increased iron requirements
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Megaloblastic Anemia
• Caused by deficiency of vitamin B12 or folic acid
• Vitamin B12 deficiency
• Pernicious anemia
• Lack of gastric intrinsic factor
• Atrophic gastritis
• Folic acid deficiency
• Inadequate intake in diet or malabsorption caused by intestinal disease
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Megaloblastic Anemia (Cont’d)
• Bone marrow
• Hypercellular, numerous megaloblasts
• Peripheral blood
• Macrocytic anemia
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Megaloblastic Anemia (Cont’d)
• Fatigue, shortness of breath, weakness
• Destruction of posterior & lateral columns in spinal cord: results in
loss of sense of vibration, proprioception, & loss of deep tendon
reflexes
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Hemolytic Anemia
• Increased red blood cell destruction (hemolysis)
• Intracorpuscular defects
• Structural abnormalities
• Sickle cell anemia, thalassemia, hereditary spherocytosis
• Extracorpuscular defects
• Antibodies, infectious agents, mechanical factors
• Autoimmune hemolytic anemia, hemolytic disease of newborn, transfusion
reactions, malaria, hemolytic anemia caused by cardiac valve prosthesis,
disseminated intravascular coagulation
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Hemolytic Anemia (Cont’d)
• Anemia (i.e., low erythrocyte count)
• Compensatory erythroid hyperplasia of bone marrow
• Hyperbilirubinemia, jaundice
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Sickle Cell Anemia
• Synthesis of abnormal beta chain of globin
• Most prevalent among African Americans
• Multiple infarcts in various organs
• Neurologic defects; sharp pain in bones, spleen (autosplenectomy),
extremities; retinal infarcts
• Hyperbilirubinemia, jaundice (bile stones)
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Sickle Cell Anemia (Cont’d)
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Hereditary Spherocytosis
• Primary defect in genes encoding either ankyrin or alpha or beta
chain of spectrin
• Most common hereditary disease of red blood cells in whites
• Autosomal dominant disease
• Peripheral blood: spherocytes, anisocytosis
• Hemolytic or aplastic crises: splenomegaly, jaundice
• Splenectomy
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Polycythemia
• Erythrocytosis
• Increased number of red blood cells
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Primary & Secondary Polycythemia
• Primary polycythemia, or polycythemia vera
• Myeloproliferative disorder
• Clonal proliferation of hematopoietic stem cells
• Uncontrolled production of red blood cells, increased total red blood
cell mass
• Secondary polycythemia
• Increased red blood cell volume as a result of erythroid bone marrow
hyperplasia caused by erythropoietin
• Usually caused by prolonged hypoxia
• Risk factors: living at high altitudes, anoxia secondary to chronic lung
disease, congenital heart disease, renal carcinoma
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Polycythemia: Symptoms
• Hypertension
• Dark red or flushed face
• Headaches, visual problems, neurologic symptoms
• Splenomegaly
• Hypercellular bone marrow
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Leukocytic Disorders
Leukocytic Disorders
Leukopenia Leukocytosis Leukemia Lymphoma
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Leukopenia
• Reduction in white blood cell count to below normal levels
• Neutropenia (agranulocytosis)
• Bacterial infections
• Lymphopenia
• Bacterial, viral, fungal, parasitic infections
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Leukocytosis
• Increased number of white blood cells in peripheral blood
• Granulocytosis (neutrophilia)
• Bacterial infection
• Eosinophilic leukocytosis (eosinophilia)
• Allergies, some skin diseases or parasitic infections
• Lymphocytosis
• Viral infections, chronic infections, some autoimmune disorders
• Splenomegaly, lymphadenopathy
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Malignant Diseases of
White Blood Cells
• Leukemias: malignant disease involving WBC precursors in
bone marrow, peripheral blood (acute & chronic)
• Myeloid
• Lymphoid
• Lymphomas: lymphoid cell malignant diseases
predominantly involving lymph nodes
• Non-Hodgkin’s lymphoma
• Hodgkin’s lymphoma
• Multiple myeloma: malignant disease of plasma cells
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Lymphoma:
Etiology and Pathogenesis
• Causes of most lymphomas, leukemias (like causes of most malignant
tumors) unknown
• Viruses
• HTLV-1
• EBV
• Endogenous oncogenes
• t(8,14): Burkitt’s lymphoma
• t(9,22): chronic myelogenous leukemia (Philadelphia chromosome)
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Leukemia
• Bone marrow: infiltrated with malignant cells
• Increased number of immature blood cells in peripheral blood
• Complications: anemia, recurrent infections, uncontrollable bleeding
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Types of Leukemias
• Acute lymphoblastic leukemia (ALL)
• Acute myelogenous leukemia (AML)
• Chronic myelogenous leukemia (CML)
• Chronic lymphocytic leukemia (CLL)
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Acute Lymphoblastic Leukemia
• Most common form of leukemia in children
• Massive infiltration of bone marrow, peripheral blood with immature
lymphoid cells (blasts)
• Symptoms: recurrent infections; generalized weakness; bleeding into
skin, major internal organs
• Treatment: modern chemotherapy; remission possible in nearly all
patients
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Acute Myelogenous Leukemia
• Most common form of acute leukemia in adults
• Clonal proliferation of myeloblasts in bone marrow (20% myeloblasts)
• Without treatment, most patients die within 6 months after
symptom onset
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Chronic Myelogenous Leukemia
(Cont’d)
• Malignant disease of pluripotent hematopoietic stem cells
• Bone marrow, peripheral blood overgrown with malignant
stem cells and descendants
• Three phases of disease:
1. Chronic phase
2. Accelerated phase
3. Blast crisis
• Treatment: tyrosine kinase inhibitors (e.g., imatinib,
“Gleevec”)
• Philadelphia (Ph1) chromosome, with BCR/ABL gene
rearrangement
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Lymphoma
• Affects any age group
• Malignant cells often infiltrate lymph nodes, spleen, thymus, or bone
marrow, but may also involve other organs
• Extranodal spread of lymphoma
• Two large categories:
1.Non-Hodgkin’s lymphoma (NHL)
2.Hodgkin’s lymphoma
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Non-Hodgkin’s Lymphomas
• No benign lymphomas
• Most have B-cell phenotype
• All age groups affected (more common in adults than children)
• Can spill over into blood; present as leukemia
• Involve lymph nodes, bone marrow, spleen, thymus, but can be of
extranodal origin
• Most common sites of extranodal lymphomas: stomach, intestines
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Burkitt’s Lymphoma
• Highly malignant tumor composed of small B cells
• Extranodal masses: more prominent than enlarged lymph
nodes
• Endemic variant:
• Sub-Saharan Africa
• Children infected with EBV
• Mandible, facial soft tissue involvement
• Sporadic variant:
• Children, young adults most often affected
• Abdominal mass (e.g., ovarian or intestinal mass)
• Most children & young adults can be cured
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Lymphoma (Cont’d)
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Staging of Hodgkin’s Lymphoma
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Hodgkin’s Lymphoma:
Clinical Features
• Enlarged lymph nodes (neck, mediastinum)
• Extranodal involvement, leukemic spread: rare
• Prognosis: depends primarily on clinical stage
• Stage I & II: excellent prognosis, high rate of cure (>90%) with chemotherapy
• Advanced disease: less favorable prognosis
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Multiple Myeloma
• Malignant disease of plasma cells
• Most patients older than 45 years
• Malignant plasma cells typically proliferate in bone marrow, destroy
surrounding bone (bone fractures)
• Renal failure
• Anemia, leukopenia
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Multiple Myeloma (Cont’d)
• Diagnosis based on:
• X-ray studies (lytic lesions)
• Serum electrophoresis (monoclonal spike)
• Bone marrow biopsy (neoplastic plasma cells in increased numbers)
• Survival rate: < 3–4 years from diagnosis; most die of kidney failure,
infection
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Hemophilia
• Sex-linked congenital clotting factor deficiency
• Hemophilia A: deficiency of factor VIII
• Hemophilia B: deficiency of factor IX
• Uncontrollable bleeding after trauma
• Subcutaneous hematomas or hemarthrosis
• Prolonged aPPT (prothrombin time normal)
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