Blood Disorders Lecture 8 PDF

Blood Disorders and Diagnostic Tests 1. White and Red Blood Cell Disorders Two major divisions of white blood cell diseases Leukemia Lymphoma Primary red blood cell abnormality Anemia Pixabay.com  2. Hematopoiesis Each blood cell type is a p...

Blood Disorders and Diagnostic Tests 1. White and Red Blood Cell Disorders Two major divisions of white blood cell diseases Leukemia Lymphoma Primary red blood cell abnormality Anemia Pixabay.com  2. Hematopoiesis Each blood cell type is a product of a specific type of parent cell Hematopoietic stem cell begins the Wikimedia Commons, 2024 process 3. White Blood Cells Neutrophils Eosinophils Basophils Monocytes Lymphocytes Pixabay.com ❖Abnormal conditions involving myeloid and lymphoid cells are leukemia (bone marrow and blood) and lymphoma (lymphoid tissues) White Blood Cell Disorders - Leukemias 4. Leukemias Malignant diseases of the bone marrow and blood Abnormal, nonfunctional white blood cells are released into circulation Two types: ❖Acute leukemias Undifferentiated (blasts) WBC in circulation ❖Chronic leukemias Immature WBC in circulation Compromised function (infections) Wikimedia Commons, 2024 Acute Leukemias 4.1 Types of Leukemias and Useful Biochemical Tests 1. Acute lymphocytic leukemia (ALL) Or lymphoblastic leukemia The most common type among children and adolescents Lymphoid precursors proliferate and replace normal cells Pixabay.com Many patients have disseminated intravascular coagulation (DIC) Bleeding Laboratory Considerations: Neutropenia, anemia, and thrombocytopenia Increased lactate dehydrogenase (LDH) Increased uric acid levels 4.1 Types of Leukemias and Useful Biochemical Tests 2. Acute myeloid leukemia (AML) Or acute myelogenous leukemia Abnormal myeloid cell precursors – no mature myelocytes, red blood cells and platelets Abnormal cells accumulate in the bone marrow, blood, spleen and liver Genetic factors (e.g., chromosomal translocations) Laboratory Considerations Neutropenia, anemia and thrombocytopenia Increased lactate dehydrogenase (LDH) and uric acid levels Diagnosis is dependent on bone marrow biopsy At east 20% blasts Chronic Leukemias 4.1 Types of Leukemias and Useful Biochemical Tests 3. Chronic lymphocytic leukemia (CLL) The most common form in adults in western countries Small, nonfunctional lymphocytes It may be asymptomatic for several years Laboratory considerations: No specific clinical biochemical tests for Pixabay.com diagnosing or confirming CLL A bone marrow biopsy and flow cytometry may be used to establish the diagnosis Most cases: abnormal B lymphocytes 4.1 Types of Leukemias and Useful Biochemical Tests 4. Chronic myeloid leukemia (CML) Or chronic myelogenous leukemia Increased numbers of granulocytes in the bone marrow Represents 20% of all adult leukemias Laboratory considerations: Elevated uric acid levels Hallmark of CML Philadelphia (PH 1) chromosome translocation in bone marrow cells (diagnostic) Wikimedia Commons, 2024 White Blood Cell Disorders - Lymphomas 5. Lymphomas Malignancy of the lymphatic system Originate from abnormal B or T cells Unknown cause (viral infection, DNA mutations?) Two major types of lymphoma ❖Hodgkin lymphoma Originates from abnormal B cells, 5 classifications Unknown cause (Epstein-Barr) Lymph nodes contain Reed-Sternberg cells Single painless lymph node in the cervical region (1st symptom) ❖Non-Hodgkin lymphoma Originates from abnormal B or T cells, more than Wikimedia Commons, 2024 30 classifications Eight times more common than Hodgkin lymphoma Peripheral lymph nodes increase in size Peripheral blood tests – no aid in diagnosis 5.1 Lymphomas and Useful Biochemical Tests Early-stage lymphomas May have normal hematology May have normal clinical biochemistry results Disease differentiation Lymph node or bone marrow biopsy Hodgkin lymphoma – Reed-Sternberg cells Diagnosis is made by imaging studies and biopsies 6. Clinical Importance of WBC count with Differential – Leukemia and Lymphoma A component of the Complete blood count (CBC) Initial diagnosis (*leukemia) E.g., increased WBC count and abnormal differentials Subtype classification Disease monitoring Detection of complications E.g. anemia, infections, bleeding disorders Treatment adjustment Assessment of response to therapy E.g., increase in normal white blood cells Identification of recurrence LifeLabs, Ontario Red Blood Cells  6. Red Blood Cells Anemias Deficiency of red blood cells or hemoglobin in the blood What is impaired in anemia? Symptoms Weakness Dizziness Pale mucous membranes Lightheadedness Tachycardia Classification of anemias Size and shape of red blood cell (i.e., microcytic, normocytic, and macrocytic) Amount of hemoglobin (i.e., hypochromic, normochromic, and hyperchromic) 6.1 Anemia- Basic Concepts 1. Hemoglobin Globular protein that transports O2 and CO2 Major structural protein of the red blood cell Complex structure (4 globin chains) Each has a molecule of heme 2. Iron Vital component of hemoglobin Also found in myoglobin, stored in tissues and in enzymes Iron absorption in intestines is regulated by a negative feedback loop (animal source Vs. plant source) Iron must be transported to the liver for heme synthesis Transferrin (important clinically) Storage: Ferritin (important clinically; liver, spleen and bone marrow) 6.1 Anemia - Basic Concepts 3. Heme Molecule composed of porphyrin and an iron atom The oxygen molecule binds to a heme group Most heme is synthesized in developing RBCs in bone marrow The heme created by the red cells is used to synthesize hemoglobin Also found in the cytochromes in mitochondria 6.2 Consequences of iron deficiency Decreased levels of iron Small RBCs (microcytes) Decreased amount of hemoglobin (hypochromia) Decreased function of cytochrome in mitochondria 6.2 Anemia and CBCs CBCs include: RBC or erythrocyte count Hemoglobin Hematocrit RBC indices: 1. Mean corpuscular volume (MCV) Average size of RBCs 2. Mean corpuscular hemoglobin (MCH) Average amount of hemoglobin per RBC 3. Mean corpuscular hemoglobin concentration (MCHC) Average concentration of hemoglobin in a volume of RBCs 4. Red cell distribution width (RDW) Indicates the degree of abnormal variation in size (anisocytosis) Anemias 6.3 Anemias and Diagnostic tests Iron-deficiency anemia Insufficiency of iron in the blood to support red cell production A type of microcytic anemia Mean corpuscular volume (MCV) is low CBC and differential results may lead to suspected anemia Hemoglobin (low), hematocrit (low), MCH (low), MCHC (low), RDW (High) Additional tests are required to make the diagnosis Iron level Total iron binding capacity (TIBC) Total amount of iron that can be bound by transferrin in the blood Ferritin 6.3 Anemias and Diagnostic tests Pernicious anemia A macrocytic anemia that results from a deficiency of vitamin B12 Fewer red blood cells carry oxygen Autoimmune disease (most cases) that causes gastric atrophy Destruction of stomach cells that produce intrinsic factor Hemolytic disorder associated with increased turnover of bilirubin Laboratory considerations Markedly increased LDH levels Elevated indirect (unconjugated) bilirubin values Normal Normal Normal Pernicious anemia 6.3 Breakdown of Hemoglobin Increased hemoglobin breakdown produces bilirubin Increased unconjugated bilirubin in plasma In circulation Most bilirubin is from destruction of old red blood cells The unconjugated bilirubin is transported to the liver by albumin Unconjugated bilirubin is converted to conjugated bilirubin in the liver Excretion into the bile Bilirubin is converted by bacteria in intestine 6.3 Anemias and Diagnostic Tests Sickle cell anemia Consequence of sickle cell disease Inherited blood disorder (mutation in hemoglobin gene) Abnormal hemoglobin Homozygous hemoglobin S (HbS) (2 copies of the gene) HbS molecules “stick” together cause red blood cell deformation (sickle shape) Cells are destroyed in the spleen – chronic anemia “Hemolytic crisis”- rapid hemolysis Elevated unconjugated bilirubin levels Laboratory considerations Sickling tests and electrophoresis Wikimedia Commons, 2024 6.3 Anemias and Diagnostic Tests Thalassemia Group of inherited blood disorders Mutations in genes that encode for alpha/beta- globin chains in hemoglobin The more genes affected the more severe Two primary types: Alpha-thalassemia and beta-thalassemia Anemia is a symptom of thalassemia Laboratory considerations Decreased hemoglobin (Hb) levels Depending on severity Reduced RBC count and size (MCV) Hemoglobin electrophoresis Genetic testing (specific genetic mutation) 6.3 Anemias and Diagnostic Tests Anemia of chronic diseases (or chronic inflammation) Classified as normocytic, normochromic anemias Associated with long-standing chronic disorders E.g., Rheumatoid arthritis, diabetes mellitus, heart disease Laboratory considerations Decreased overall RBC count Decreased levels of iron in blood Decreased erythropoietin production Decreased red blood cell life span (70 to 80 days)