Blood Components Notes - Hanson PDF

Blood Components ​ Blood is divided into: ○​ Plasma (Plasma Proteins): ​ Plasma proteins (globulins) are synthesized in the liver (except ɣ-globulins) ​ ɑ and Β globulin make hemoglobin — role in transportation ​ ɣ globul...

Blood Components ​ Blood is divided into: ○​ Plasma (Plasma Proteins): ​ Plasma proteins (globulins) are synthesized in the liver (except ɣ-globulins) ​ ɑ and Β globulin make hemoglobin — role in transportation ​ ɣ globulin are immunoglobulins ​ Albumin contributes to ~70% of total plasma protein ○​ Role in osmotic pressure of the blood ○​ Ability to bind to certain drugs ​ Role of Plasma Proteins in Capillary Exchange: ​ Colloid Osmotic Pressure pulls fluid INTO the capillary ​ Hydrostatic pressure forces fluid OUT of the capillary ○​ Problems with the movement of fluids can cause EDEMA ○​ Hematopoietic Cells are comprised of platelets, RBC, and WBC ​ Platelets (Thrombocytes): ​ Conduct blood clotting ​ White Blood Cells (Leukocytes): 2 major categories ​ Granulocytes: Neutrophils, Eosinophils, and Basophils ​ Agranulocytes: Lymphocytes and Monocytes ​ Red Blood Cells (Erythrocytes) ​ Hematocrit is the percentage of red blood cells in whole blood ​ RBCs circulate for 120 days Hematopoiesis: ​ Process of NEW blood cell formation in the BONE MARROW derived from MULTIPOTENT HEMATOPOIETIC STEM CELLS ○​ IMPORTANCE? Multipotent hematopoietic stem cells go down different pathways to develop a blood cell into a more specialized hematopoietic cell. ○​ HOW? Through hematopoietic growth factors. ​ Hematopoietic growth factors are PROTEINS that bind to receptors and stimulate hematopoietic stem cells. ​ Types of Hematopoietic Growth Factors: ○​ Erythropoietin (EPO) stimulate erythrocyte production ​ Pharmacologic agents that stimulate Erythropoiesis ​ Recombinant human EPO: ○​ Epoetin alfa (Epogen/Procrit) ○​ Darbepoetin Alfa (Aranesp) ​ HIF Prolyl Hydroxylase Inhibitors: ○​ Daprodustat ○​ Roxadustat ○​ Vadadustat ○​ Thrombopoietin stimulate platelet production ​ Thrombocytopenia is low platelet count with increased risk of bleeding ​ Pharmacologic agents that stimulate Thrombopoiesis ​ Oprelvekin (Neumega) ​ Romiplostim (Nplate) ​ Eltrombopag (Promacta) ○​ G-CSF stimulate neutrophil production ​ Neutropenia is low neutrophil count caused by decreased production of leukocytes ​ Pharmacologic agents that stimulate Leukocyte (Neutrophil) ​ Filgrastim (Neupogen) ​ PEGfilgrastim (Neulasta) ​ Sargramostim (Leukine) Erythropoiesis: Production of Erythrocyte Production ​ Erythropoiesis REQUIRES Vitamin B12, folic acid for DNA synthesis and iron for hemoglobin synthesis ○​ Reticulocytes: Developing erythrocytes ​ Released from the bone marrow and circulates for 1-2 days before becoming MATURE ERYTHROCYTES ​ HIGH RETICULOCYTE COUNT indicate bone marrow is responding to anemia ​ LOW RETICULOCYTE COUNT indicate bone marrow problems ○​ Erythrocytes (RBCs) ​ Produced in the BONE MARROW and destroyed in the SPLEEN and LIVER ​ Low HEMOGLOBIN (Hg) levels indicate low oxygen levels in the blood ​ Low # of HEMATOCRIT is an indication of anemia ​ Agents that Stimulate vs. Inhibit Erythropoiesis: ○​ Stimulate: ​ Bleeding, hemolysis, high altitude, pulmonary disease → Induce tissue hypoxia ​ JACK-2 activating mutations → Increase JAK-STAT signaling cascade ​ Pharmacologic ○​ Inhibit: ​ Chronic kidney disease → Decrease erythropoietin synthesis ​ Iron, folate, or vitamin B12 deficiency → Decrease erythrocyte production ​ Erythropoietin (EPO) ○​ Erythropoietin, a protein hormone, is released by the kidney to regulate the production of RBCs ​ During hypoxia (decrease in oxygen), there is LOW HEMOGLOBIN → leads to more EPO and more RBC ​ IN THE KIDNEY – EPO is released into the bloodstream and travels to the BONE MARROW ​ IN THE BONE MARROW – EPO stimulates ERYTHROPOIESIS ○​ Process of EPO Stimulating Erythropoiesis: ​ 1.​ EPO interacts with the EPO receptor on the plasma membrane. ​ 2.​ Receptor undergoes a conformational change and causes JAK2 to auto-phosphorylate. ​ 3.​ Phosphorylated JAK2 phosphorylates the EPO receptor. ​ 4.​ Phosphorylated EPO receptor and JAK2 recruit and activate the STAT transcription factor and phosphorylate it. ​ 5. ​ Transcription factor moves to the nucleus and turns on genes for erythropoiesis.  ​ ○​ EPO and HIF ​ Hypoxia Inducible Factor (HIF) is a transcription factor that helps cells sense and adapt to low oxygen levels. It is DESTABILIZED by oxygen and STABILIZED by hypoxia ​ Normal Oxygen Levels: EPO production is down. ​ Prolyl hydroxylase monitors oxygen levels in the cell ○​ Prolyl hydroxylase adds a hydroxyl group on HIF-1ɑ ​ von Hippel-Lindau (VHL) protein ○​ VHL protein recognizes the hydroxylated HIF-1α and attaches a small protein called ubiquitin to it. ​ Ubiquitination ○​ Once HIF-1α is tagged with ubiquitin, proteasome identifies and breaks down HIF-1α → degradation ​ During hypoxia: EPO production is up. ​ Hif-1α does not get hydroxylated by propyl hydroxylase and is stabilized. ​ Stabilized Hif-1α goes to the nucleus and binds to Hormone Response Element (HRE) on DNA. ​ Transcription occurs and results in INCREASED EPO. ​ EPO then binds to EPO receptor on RBC precursor and leads to erythrocyte production Anemia: ​ Anemia is characterized by decreased Hb or decreased RBCs. ​ Anemia Defining Basis: ○​ Anemia can be defined on the basis of cell size (MCV – mean corpuscular volume) AND amount of Hb (MCHC – mean corpuscular Hb concentration) ​ MCV – mean corpuscular volume: ​ Microcytic anemia → lower limit ​ Normocytic anemia → normal limit ​ Macrocytic anemia → upper limit ​ MCHC – mean corpuscular Hb concentration: ​ Hypochromic anemia → lower limit ​ Normochromic anemia → normal limit ​ Hyperchromic anemia → upper limit ​ Other Measures of Testing Anemia: ○​ Transferrin Saturation: ​ Blood test that measures the amount of iron bound to transferrin, the protein that carries iron in the blood. ○​ Serum Ferritin: ​ Blood test that measures the amount of ferritin protein (protein that bind and hold onto iron) in your blood, which indicates how much iron your body stores ​ Low serum ferritin = low iron levels ​ Types of Anemia: ○​ Microcytic, Hypochromic: ​ Iron deficiency ​ Sideroblastic Anemia → due to problems with heme synthesis ​ Hereditary: X-linked sideroblastic anemia → mutations in the 1st step of heme synthesis (ALAS2 deficiency) ​ Toxin: Lead poisoning → Lead can bind to and inactivate heme ​ Nutritional: vitamin B6 deficiency ○​ Normocytic, Normochromic → due to premature RBC destruction ​ Acute Blood Loss ​ Hemolysis ​ Chronic Disease ○​ Macrocytic, Normochromic ​ Megaloblastic Anemia → Due to a defect in DNA synthesis ​ Vitamin B12 Deficiency ​ Folate Deficiency  ​ Non-megaloblastic Anemia → There is no impairment in DNA synthesis ​ Alcohol and other causes ​ Polycythemia → Abnormal overproduction of RBC that leads to higher Hg levels and high hematocrit levels ○​ Primary Polycythemia caused by factors INTRINSIC to red cell precursors ​ Polycythemia vera due to mutations in JAK2 ​ Hypersensitivity to EPO → signal for too many RBCs ​ Primary familial and congenital polycythemia (PFCP) due to mutations in EPO receptor ​ Hypersensitivity to EPO → signal for too many RBCs ○​ Secondary Polycythemia caused by factors EXTRINSIC to red cell precursors ​ Mutations in VHL, PHD, or HIF-1α Blood Types: ​ 4 Major Types of Blood: ○​ Type A produces acetylgalactosamine (A allele) ​ A antigen, B antibody ○​ Type B produces galactosyltransferase (B allele) ​ B antigen, A antibody ○​ Type AB produces both alleles ​ A + B antigen, no antibody ○​ Type O produces a DEFECTIVE transferase ​ No antigen, A + B antibody ​ Rh Incompatibility: ○​ RhoGam (anti-RhD antibodies): Prevents sensitization of the maternal immune system to D antigen. ○​ CANNOT give Rh+ blood to a Rh- ​ If already Rh+, can receive both Rh+ and Rh- ​