Hema and lymphoid

• Anemia


  Reduction in the oxygen-transporting capacity of blood, resulting from a decrease in red cell mass to subnormal levels
• Causes of anemia


  • Bleeding
  • Increased RBC destruction
  • Decreased RBC production
• Classification of anemia based on red cell morphology

  • Microcytic: iron deficiency, thalassemia
  • Macrocytic: folate, vitamin B12 deficiency
  • Normocytic but with abnormal shapes: hereditary spherocytosis, sickle cell disease
• Clinical manifestations of anemia

  • Acute: shortness of breath, organ failure, shock
  • Chronic
• Tests for red cell disorders

  • CBC - RBC indices, Hgb and RBC count
  • Peripheral Blood Smear - morphology of RBC
  • Serum Iron indices - distinguish microcytic anemia
  • Plasma Unconjugated Bilirubin, Haptoglobin, LDH - abnormal in hemolytic anemia
  • Folate and Vit B12 concentration - low in megaloblastic anemia
  • Hgb electrophoresis - detect abnormal hemoglobin
  • Coombs test - detect antibodies bound to RBC in antibody-mediated hemolytic anemia
  • Reticulocyte count - distinguishes between hemolytic and aregenerative anemia

  
• Iron indices


  • Serum Iron
  • Ferritin
  • TIBC
  • Transferrin
• Red cell indices


  • Mean Cell Volume (MCV): average vol per red cell; femtoliters
  • Mean Cell Hemoglobin (MCH): average mass of hemoglobin per red cell; picograms
  • Mean Cell Hemoglobin Concentration (MCHC): average concentration of hgb in a given volume of packed red cells; g/dL
  • Red Cell Distribution Width: coefficient of variation of red cell vol
• Anemia of blood loss: Acute bleeding


  Due to the loss of intravascular volume, which if massive can lead to cardiovascular collapse, shock and death
• Anemia of blood loss: Recovery

  Hemodilution begins at once (2-3 days); Compensatory Inc erythropoietin -> Inc RBC production (5-7 days)
• Blood loss >20% of BV = hypovolemic shock NOT anemia
• Anemia of blood loss: Chronic bleeding

  Iron stores are gradually depleted
• Hemolytic anemia


  Erythroid hyperplasia & Reticulocytosis: hallmarks of HA
• Types of hemolytic anemia

  • Hereditary Spherocytosis
  • Sickle Cell Anemia
  • Thalassemia
  • Glucose-6-Phosphate Dehydrogenase Deficiency
  • Immunohemolytic Anemia
• Hereditary Spherocytosis


  • Inherited defects in the membrane skeleton (ankyrin, spectrin) that stabilizes the lipid bilayer of RBC
  • Smear: dark red, lack central pallor, Howell-jolly bodies
  • Splenomegaly
• Sickle Cell Anemia


  • Autosomal recessive
  • Mutation in β- globin that causes deoxygenated hgb to self-associate into long polymers
  • Val -> Glu
  • Pain crises and tissue infarction due to blockage of vessels
  • Moderate splenomegaly
  • Common to infection
  • Malaria
• Thalassemia


  • Autosomal codominant
  • Mutation in globin synthesis: Alpha or Beta chains deficient synthesis
  • Microcytosis, hypochromia, poikilocytosis, anisocytosis, nucleated RBCs
  • Skeletal deformities, cachexia, splenomegaly
  • Alpha Thalassemia: -/α,α/α : silent carrier, -/-,α/α : α thalassemia trait, -/-,-/α : HbH disease, -/-,-/- : Hydrops fetalis
  • Beta Thalassemia: Major : homozygous B-thalassemia, Intermedia : variable, Minor : heterozygous B-thalassemia
• G6PD Deficiency


  • X-linked
  • Mutations that destabilize G6PD, making RBC susceptible to oxidant damage
  • Heinz bodies and Bite cells
• Immunohemolytic Anemia


  • Caused by Antibodies against normal RBC constituents or antigens modified by haptens
  • RBC opsonization, extravascular or intravascular hemolysis
• Anemias of diminished erythropoiesis

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


  • Most common nutritional deficiency in the world
  • Caused by chronic bleeding or inadequate iron intake
  • Predominantly vegetarian diets
  • Microcytic, hypochromic
  • Dec Iron and Ferritin; Inc TIBC
• Anemia of Chronic Inflammation


  • Most common form of anemia in hospitalized patients
  • Caused by inflammatory cytokines, which increase hepcidin levels
  • Slightly hypochromic and microcytic
  • Inc Iron and Ferritin; Dec TIBC
• Megaloblastic Anemia


  • Caused by deficiencies of folate or vitamin B12
  • Inadequate synthesis of thymidine and defective DNA replication
  • Results: enlarged abnormal hematopoietic precursors, ineffective hematopoiesis, macrocytic anemia and pancytopenia
  • Hypersegmented neutrophils, egg shaped macroovalocytes
• Aplastic Anemia


  • Disorder in which multipotent myeloid stem cells are suppressed
  • Caused by bone marrow failure
  • Causes: toxins, radiation, drugs, viruses, telomerase defects
• Myelophthisic Anemia


  • Cause by extensive infiltration of the marrow by tumors or other lesions
  • Associated with metastatic breast, lung, prostate CA
  • Teardrop RBC
• Polycythemia vera


  • Erythrocytosis: increase in RBC per unit volume of peripheral blood
  • ALL cell lines increased, not just RBC
  • Absolute (increase in total red cell mass)
  • Relative (dehydration)

  
• White cell disorders


  • Deficiencies vs Proliferations
  • Reactive vs Neoplastic
  • Leukemias
  • Lymph nodes
  • Spleen/Thymus

  
• Leukopenia


  Decrease in WBC
• Neutropenia/Agranulocytosis


  Decreased in granulocyte production, increased granulocyte destruction; <500 cells/uL
• Reactive leukocytosis


  • Increase in WBC, 12,000-18,000 cells/Ul
  • Neutrophilia, Eosinophilia, Basophilia, Monocytosis, Lymphocytosis
• Reactive lymphadenitis


  Activated by infections and nonmicrobial inflammatory stimuli
• Pelger-Huet Anomaly


  • Autosomal Dominant
  • All neutrophils look like BANDS
• Chediak-Higashi Syndrome


  • Autosomal Recessive
  • Abnormal LARGE irregular neutrophil granules
  • Impaired lysosomal digestion of bacteria
• Broad categories of neoplastic proliferations of WBC

  • Lymphoid neoplasms: leukemia, non-Hodgkin, Hodgkin lymphoma
  • Myeloid neoplasms: leukemia, Myelodysplastic syndrome, Myeloproliferative Neoplasms
  • Histiocytic neoplasms: Langerhans cell histiocytoses, proliferative lesions of macrophages and dendritic cells
• Lymphoid neoplasms


  • Classification is based on cell of origin and stage of differentiation
  • Most common types in children: ALLs, Lymphoblastic lymphoma from precursor B and T cells
  • Most common types in adults: non-Hodgkin lymphomas derived from germinal center B cells

  
• Myeloid neoplasms


  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • Myeloproliferative neoplasms
  • Chronic Myeloid Leukemia
• Acute Myeloid Leukemia


  • Aggressive tumors comprised of immature myeloid lineage
  • Auer rods, blasts accumulate in the bone marrow
• Chronic Myeloid Leukemia


  • Presence of BCR-ABL gene derived from portions of BCR gene on chromosome 22 and ABL gene on chromosome 9
  • Predominantly neutrophils, metamyelocytes, myelocytes
• Myelodysplastic Syndrome


  • Group of clonal stem cell disorder characterized by maturation defects that are associated with ineffective hematopoiesis
  • Increase in 1 or more formed elements; ring sideroblasts
• Myeloproliferative neoplasms


  • Production of formed myeloid elements is initially increased, leading to high blood counts and extramedullary hematopoiesis
  • Dysplastic marrow precursors and peripheral blood cytopenia

  
• Bleeding disorders


  • Disseminated Intravascular Coagulation
  • Immune Thrombocytopenic Purpura
  • Thrombotic Thrombocytopenic Purpura
  • Hemolytic Uremic Syndrome
  • Von Willebrand Disease
  • Hemophilia