Hematolymphoid 2 Flashcards
How is iron absorbed, transported, stored
- Absorbed in small intestine → bound to transferrin and transported → incorporated into hemoglobin
- Stored in ferritin (aggregates as hemosiderin)
- Aging RBCs destroyed in the spleen and iron reutilized
Causes of iron deficiency anemia
- Decreased intake
- Decreased absorption
- Increased loss
- Increased requirements
Iron deficiency anemia lab results
- Blood smear: hypochromic microcytic anemia
- Hemoglobin and hematocrit low
- Serum iron and ferritin low
Aplastic anemia
Characterized by loss of multipotent stem cell resulting in pancytopenia
- Decreased RBC = anemia
- Decreased WBC = infection prone
- Decreased platelets = bleeding
Aplastic anemia causes
Primary: Idiopathic
Secondary (related to BM suppression):
- Chemical agents (cytotoxic drugs)
- Radiation
- Viral infection
- Inherited
Megaloblastic anemia
Caused by deficiency of vitamin B12 or folic acid (essential for DNA synthesis and blood cell production)
Megaloblastic anemia pathogenesis
- Deficiencies delay normal RBC maturation
- RBC precursors do not mature and are transformed into megaloblasts
- Megaloblasts are destroyed in BM or spleen
Megaloblastic anemia diagnosis
Diagnosis
- Peripheral blood smear: oval macrocytes, large segmented neutrophils
- BM biopsy: hypercellular with megaloblasts
Causes of Vitamin B12 deficiency
- Decreased intake (uncommon)
- Impaired absorption/increased loss (Pernicious anemia)
Pernicious anemia pathogenesis
Atrophic gastritis → results in decrease in gastric parietal cells → insufficient IF → B12 deficiency → megaloblastic anemia
Results of folate deficiency
Results in megaloblastic anemia (similar characteristics as B12 deficiency)
Causes of folate deficiency
- Impaired absorption/increased loss (Disease of duodenum)
- Decreased intake
- Increased requirement
Thalassemias
Genetic defect in synthesis of normal Hb (no abnormal Hb is produced, defect is quantitiative)
Thalassemia classifications
Classified by type of chain affected
- a thalassemias → defecetive a chain synthesis
- b thalassemias → defecetive b chain synthesis
a thalassemia
What types?
- Single gene deletion → silent carrier (asymptomatic)
- 2 gene deletion → a thalassemia trait (mild anemia)
- 3 gene deletion → Hemoglobin H disease (moderate to severe anemia; HbH tetramer of B globulins forms → poor O2 delivery → HbH sequestering/destruction in spleen)
- 4 gene deletion → Hydrops fetalis (most severe; excess y chains form tetramers → poor O2 delivery → fetus death)
B thalassemia
What types?
- Thalassemia minor (heterozygote) → mild, nonspecific symptoms
- Thalassemia major (hommozygote) → severe, decreased RBC production and unpaired a chains prone to hemolysis/precipitation
Sickle cell disease
Group of inherited disorders of Hb due to defect in B globin gene
- In low O2 states, abnormal Hb polymerizes making RBCs sickle
- Results in chornic hemolytic anemia and small vessel occlusion
Cause of sickle cell disease
- Point mutation in B globin gene → aa substitution → abnormal B chain
Sickle cell anemia
Homozygous for defective gene
- HbS < 40% → asymptomatic
- HbS 40-80% → mild to moderate
- HbS 80% → severe
Sickle cell trait
Heterozygous for defective gene
- <40% Hb is Hbs, thus cells do not sickle and patients are asymptomatic
Hereditary spherocytosis
Group of genetic defect characterized by defect of structural proteins in RBC (most are autosomal dominant)
- Defective RBCs unable to maintain biconcave shape (spheres) and are removed by the spleen
Clinical findings of hereditary spherocytosis
Anemia, splenomegaly, jaundice
Polycythemia
(Erythrocytosis) → An increase in the number of RBCs
Relative polycythemia causes
Hemoconcentration (dehydration)
Absolute polycythemia causes
Primary (low erythropoietin):
- Polycythemia rubra vera (uncontrolled production of RBCs due to myleoproliferative disorder)
Secondary (high erythropoietin):
- Living at high altitude; chronic lung disease
Polycythemia symptoms
Increased viscosity (sluggish blood flow and tendency to clot)
Leukocytosis
Increased number of WBCs
- Typically benign
- Often associated with splenomegaly or lymphadenopathy
Types of leukocytosis and effects
Neutrophilic leukocytosis (increased neutrophils) → acute bacterial infections
Eosinophilic leukocytosis (increased eosinophils) → parasites, allergies, drug reaction
Lymphocytosis (increased lymphocytes) → viral infections, chronic infections (e.x. TB)
Leukopenia
Reduction in WBC count
Types of leukopenia
Neutropenia and lymphopenia
Neutropenia (Leukopenia)
Decreased number of neutrophils → susceptible to bacterial infection
Neutropenia (Leukopenia) Causes
- Ineffective granulopoiesis (e.x. aplastic anemia)
- Accelerated removal or destruction of neutrophils (e.x. Ab destruction by SLE)
Lymphopenia (Leukopenia)
Decreased number of lymphocytes (selective lymphopenia = decreased subset of lymphocytes)
Lymphopenia (Leukopenia) causes
- Ineffective hematopoeisis
- Accelerated removal or destruction of lymphocytes
Acute Lymphoblastic Leukemia
- Prevelance: 20% (most common type in children)
- BM infiltrated with immature lymphoid cells spill over into blood
- Lethal without chemotherapy
Acute Myelogenous Leukemia
- Prevelance: 40% (most common type in adults)
- BM infiltrated by immature myeloid cells spill over into blood
- Classified by WBC linneages affected
- Lethal without treatment (chemotherapy, radiotherapy, BM transplant)
Chronic Myelogenous Leukemia
- Prevelance: 15% (incidence increases with age)
- BM infiltrated by myeloid cells
- Characterized by Philadelphia chromosome
- Slow insidious onset, asymptomatic
- 3 phases: chronic phase → accelerated phase → blast crisis
Chronic Lymphocytic Leukemia
- Prevalence: 25% (Elderly, slow progression)
- BM infiltrated by lymphoid cells, spills into blood
- Involves LNs/spleen → small lymphocutic lymphoma
- CLL cells grow slowly
Hodgkin Lymphoma
- Biomodal age distribution (25; 55)
- 5 types
- Staging is key for prognosis
- Chemotherapy effective
Hodgkin lymphoma types
Classical HL (90%) (presence of Reed Sternberg cell → malignant B cell):
- Nodular slcerosis HL (70%)
- Mixed cellularity HL (20%)
- Lymphocyte-rich HL (5%)
- Lymphocyte-depleted HL (5%)
Nodular lymphocyte predominant of HL (10%)
Multiple myeloma age group
Middle age (>45)
Multiple myeloma
Malignant disease of plasma cells
- Plasmacytoma = single lesion (can be of bone or extramedullary (soft tissue))
Multiple Myeloma pathogenesis
Malignant transformation of single plasma cell → clonal expansion → monoclonal expansion of plasma cells → secrete monoclonal Ig’s
Multiple myeloma clinical features
CRAB:
- C = Calcium (Hypercalcemia → calcium released from destroyed bones)
- R = Renal failure (Ig’s excreted damage renal tubes; hypercalcemia damages kidneys)
- A = Anemia (replacement of normal BM by tumor)
- B = Bone lesions (lytic bone lesions caused by plasma cells)
Bleeding Disorders
Vascular disorders or Platelet disorders
Vascular disorders (Bleeding disorders)
- Common cause: mechanical trauma
- Vessel wall fragility (old age, connective tissue disorder)
- Immune damage (vasculitis)
Types of platelet disorders (Bleeding disorders)
Qualitative or quantitative
Quantitative platelet disorder (bleeding disorders)
- Decreased production (aplastic anemia)
- Increased destruction (autimmune disorders)
- Increased utilization (disseminated intravascular coagulation)
Qualitative platelet disorder (bleeding disorders)
Acquired: NSAIDs and aspirin
Congenital:
- Defect platelet adhesion (Benard-Souilver syndrome)
- Defective platelet aggregation (Glanzmann thrombasthenia)
