Lecture 3 hematopoietic_function.pdf

Chapter 3 Hematopoietic Function LEARNING OBJECTIVES ▪ Discuss normal hematopoietic function. ▪ Describe and compare diseases of the white blood cells. ▪ Describe and compare diseases of the red blood cells. ▪ Describe and compare diseases of the platelets. ...

Chapter 3 Hematopoietic Function LEARNING OBJECTIVES ▪ Discuss normal hematopoietic function. ▪ Describe and compare diseases of the white blood cells. ▪ Describe and compare diseases of the red blood cells. ▪ Describe and compare diseases of the platelets.  Hematopoiesis ▪ Process of forming blood ▪ Occurs primarily in the bone marrow ▪ Plasma - liquid protein ▪ Leukocytes - white blood cells ▪ Erythrocytes - red blood cells ▪ Hemoglobin: oxygen carrying component ▪ Hematocrit: amount of blood volume occupied by erythrocytes ▪ Thrombocytes - platelets  Table: Summary of Blood Cells Chiras, D. (2011). Human biology (7th ed.). Sudbury, MA: Jones & Bartlett Learning.  Hemostasis ▪ Stoppage of blood flow ▪ Normal when it seals a blood vessel to prevent blood loss and hemorrhage ▪ Abnormal when it causes inappropriate clotting or when clotting is insufficient to stop blood flow.  Stages of Hemostasis 1. Vessel spasm 2. Formation of a temporary platelet plug 3. Blood coagulation (results in the formation of fibrin, a protein that forms a mesh-like network around the platelet plug to form a stable blood clot) 4. Clot retraction (shrink to pull the edges of the damaged blood vessel together and promote healing) 5. Clot dissolution (fibrinolysis “the breakdown of fibrin by an enzyme called plasmin)  Figure: Blood clotting Story, L. (2012). Pathophysiology: A practical appraoch. Jones & Bartlett Learning: Burlington, MA. Disorders of the WBCs Leukocytes key players in the inflammatory response and fighting infections Normal range = 5,000 to 10,000 mm3 Leukopenia: decreased levels (immunodeficiency) Leukocytosis: increased levels (infections) WBCs escape from the capillary wall and migrate to the site of infection. Once they get to the site, WBCs phagocytize microorganisms, preventing the infection from spreading. Neutrophils One type of leukocytes Usually the first to arrive at the site of infection Normal range is 2,000–7,500 cells/mL neutrophils phagocytize microorganisms, preventing the infection from spreading. As the neutrophils are fully utilized, the infected cells die and become part of the yellowish wound drainage, or pus. Figure: The role of neutrophils Neutropenia Neutrophils < 1.500 cells/mL The lower the neutrophil count, the less the body’s ability to fight infections.  Causes ▪ Increased usage (infection & inflamm.) ▪ Drug suppression (e.g. immunosuppressants & chemotherapies) ▪ Radiation therapy ▪ Congenital conditions (e.g., periodic or cyclic: 3-5 days every 21 days, Mutation in ELANE gene which provides instructions for making a protein called neutrophil elastase)  Causes ▪ Bone marrow cancers (e.g., leukemias & lymphomas) ▪ Spleen destruction (e.g., Felty’s syndrome: ‘SANTA” Mnemonic S: splenomegaly A: anemia N: neutropenia T: thrombocytopenia A: arthritis) ▪ Vitamin deficiency (B12 & folate)  Neutropenia Manifestations – Depends on severity and cause – Infections and ulcerations especially of the respiratory tract, skin, vagina, and gastrointestinal tract – Signs and symptoms of infection (e.g., fever, malaise, and chills) Diagnosis: neutrophil levels and bone marrow biopsy Treatment: Antibiotic therapy and hematopoietic growth factors Infectious Mononucleosis “Kissing Disease”: oral transmission Self-limiting Most prevalent in adolescents and young adults Caused by Epstein-Barr virus in the herpes family EBV infects the B cells by killing the cell or being incorporated into its genome → B cells produce heterophile antibodies Once the disease is eliminated, a few B cells remain altered, giving the individual an asymptomatic infection for life and occasional spreading the EBV to others Infectious Mononucleosis Manifestations – Insidious onset – Incubation = 4 to 8 weeks – Initially see anorexia, malaise, & chills – Manifestations intensify to include leukocytosis, fever, chills, sore throat, & lymphopathy – Acute illness usually last 2-3 weeks; may not fully recover for 2-3 months Treatment: symptomatic and supportive  Erythrocyłe Nøuøophll Eosinc›pŁńI Mcæoblast Monocytø LympŁ¥ncyla Lymphoblasł Lymphomas ▪ Cancers affect lymphatic system ▪ Most common hematologic cancer in the US ▪ is the eighth most common cancer in adults ▪ Is the fifth most common cancer in children. ▪ Two main types ▪ Hodgkin’s ▪ Non-Hodgkin’s Hodgkin’s Lymphoma Less common of the two Occurs primarily in adults 20–40 years of age Solid tumors with the presence of Reed- Strenberg cells (Hodgkin cells): larger abnormal B cells. Typically originate in the lymph nodes of the upper body (e.g., the neck, chest, and upper arms) Systemically, the cancer cells spread from one lymph node to the next through the lymphatic vessels Very curable with treatment Manifestations: painless enlarge nodes, weight loss, fever, night sweats, pruritus, coughing, difficulty breathing, chest pain, recurrent infections, and splenomegaly  Reed- Normal Sternberg lymphocyte Cell @ Comstock Images/age fotostock. Copyright 0¢ 2015 by Jones & Bartlett Learning, LLC an Ascend Learning Company www.jbIearning.cam Hodgkin’s Lymphoma Staging Stage I: The lymphoma cells are in one lymph node group or one part of a tissue or an organ. Stage II: The lymphoma cells are in at least two lymph node groups on the same side of the diaphragm, or the lymphoma cells are in one part of a tissue or an organ and the lymph nodes near that organ. Stage III: The lymphoma cells are in lymph nodes above and below the diaphragm. Lymphoma cells may be found in one part of a tissue or an organ near these lymph node groups. Cells may also be found in the spleen. Stage IV: Lymphoma cells are found in several parts of one or more organs or tissues, or the lymphoma cells are in an organ and in distant lymph nodes. Recurrent: The disease returns after treatment. © Jones & Bartlett Learning Hodgkin’s Lymphoma Diagnosis: physical examination, presence of Reed-Sternberg cells in a lymph node biopsy, complete blood count, chest X-rays, computed tomography scan, magnetic resonance imaging, positron emission tomography scan, and bone marrow biopsy Treatment: chemotherapy, radiation, and surgery Non-Hodgkin’s Lymphoma More common Start at any age and in any lymph node Poor prognosis Non-Hodgkin’s lymphoma involves multiple nodes scattered throughout the body and metastasizes in an unorganized manner Similar to Hodgkin’s manifestations, staging, and treatment BUT different in the spread and diagnosis Can originate in the T or B cells No Reed-Sternberg cells Leukemia ▪ Cancer of the leukocytes ▪ Is the second most common blood cancer. ▪ Is the most common cancer among children ▪ Leukemia cells (abnormal leukocytes) proliferate (don not die), crowding normal blood cells; makes it difficult for normal blood cells to function properly.  Risk Factors ▪ Men are more likely to develop leukemia than are women. ▪ Exposure to chemical, viral, and radiation mutagens ▪ Smoking ▪ Use of chemotherapies ▪ Certain disease conditions (e.g., Down syndrome) ▪ Immunodeficiency disorders. Types of Leukemia Acute lymphoblastic leukemia (ALL) – Affects primarily children – Responds well to therapy – Good prognosis Acute myeloid leukemia (AML) – Affects primarily adults – Responds fairly well to treatment – Prognosis somewhat worse than that of ALL Types of Leukemia Chronic lymphoid leukemia (CLL) – Affects primarily adults – Responds poorly to therapy, yet most patients live many years after diagnosis Chronic myeloid leukemia (CML) – Affects primarily adults – Responds poorly to chemotherapy, but the prognosis is improved with allogenic bone marrow transplant Leukemia Manifestations: leukopenia, anemia, thrombocytopenia, lymphadenopathy, joint swelling, bone pain, weight loss, anorexiam hepatomegaly, splenomegaly, and central nervous system dysfunction Diagnosis: a history, physical examination, peripheral blood smears, complete blood count, and bone marrow biopsy Treatment: chemotherapy and bone marrow transplant Multiple Myeloma ▪ Plasma cell (producing antibodies) cancer. ▪ Uncontrolled growth ▪ Most often affects older adults ▪ Is the third most common blood cancer. ▪ Excessive numbers of abnormal plasma cells in the bone marrow crowd the blood- forming cells and cause Bence Jones proteins to be excreted in the urine. ▪ Bone destruction (osteoclasts) leads to hypercalcemia and pathologic fractures ▪ Often well advanced upon diagnosis Multiple Myeloma Manifestations – Insidious onset – Include: anemia, thrombocytopenia, leukopenia, decreased bone density, bone pain, hypercalcemia, and renal impairment Diagnosis: serum and urine protein, calcium, renal function tests, complete blood count, biopsy, X-rays, computed tomography, and magnetic resonance imaging Treatment: chemotherapy & complication management Disorders of the RBCs Erythropoiesis: Production of erythrocytes Regulated by erythropoietin Occurs in bone marrow ▪ The normal range is 4.2–5.9 million cells/μL) ▪ Disorders typically result from a deficit (quantity) or defect (quality) in the erythrocytes  Committed Normoblast Reticulocyte Erythrocyte mitted proerythroblast (nucleus shrinks (oell leaves marrow (oell achieves final pluripotential and is reabsorbed) and enters blood- size and shape: stem stream) hemoglobin cell synthesis ceases) Erythropoietin Fig. Erythrocyte Differentiation. Erythrocyte differentiation from large, nucleated stem cell to small, nonnucleated erythrocyte. @ Comstock Images/age fotostock. Copyright 0¢ 2015 by Jones & Bartlett Learning, LLC an Ascend Learning Company www.jbIearning.cam  Anemia Acquired or Inherited disorder of the erythrocytes that impairs the oxygen- carrying capacity of the blood leading to tissue hypoxia. Results from decreased number of circulating erythrocytes (blood loss or ↓ production), reduction of hemoglobin, or abnormal hemoglobin Several types with varying etiology General manifestations: weakness, fatigue, pallor, syncope, dyspnea, and tachycardia Diagnosis of Anemia Anemia is diagnosed when: hematocrit is less than 41% in males and less than 37% in females hemoglobin concentration falls to less than 13.5 g/dL in males and less than 12 g/dL in females.  Iron-Deficiency Anemia ▪ The most common in the world ▪ Iron is necessary for hemoglobin production ▪ Is most commonly seen in women of childbearing age, children younger than 2 years of age, and the elderly ▪ Causes: decreased iron consumption, decreased iron absorption, and increased bleeding ▪ Additional manifestations: cyanosis to sclera, brittle nails, decreased appetite, headache, irritability, stomatitis, pica, and delayed healing ▪ Diagnosis: complete blood count (↓ hemoglobin, hematocrit, MCV, and MCHC), serum ferritin, serum iron, and transferring saturation) ▪ Treatment: identify and treat cause, increase dietary intake, and iron supplements  Figure: Iron deficiency anemia When an iron deficiency exists, erythrocytes will become pale (hypochromic) and small (microcytic)  Pernicious Anemia ▪ Most often results from cyanocobalamin (vitamin B12 necessary for DNA synthesis & maturation of RBCs) deficiency. ▪ Occurs gradually and from a lack of intrinsic factor. ▪ Intrinsic factor is a protein produced by the stomach that is necessary for vitamin B12 to be absorbed in the stomach. ▪ The lack of intrinsic factor arises because of the actions of autoantibodies, with the subsequent immune reaction leading to atrophy of the gastric mucosa and glands. ▪ This type of anemia is characterized by large (macrocytic), immature erythrocytes (Megaloblastic Anemia ).  Pernicious Anemia ▪ Vit. B12 is required for DNA synthesis ▪ Leads to decreased maturation & cell division ▪ May see myelin breakdown & neurological complications ▪ Manifestations: bleeding gums, diarrhea, impaired smell, loss of deep tendon reflexes, anorexia, personality or memory changes, positive Babinski’s sign, stomatitis, paresthesia, and unsteady gait ▪ Diagnosis: serum B12 levels, Schilling’s test, complete blood count, gastric analysis, and bone marrow biopsy ▪ Treatment: injectable B12 Figure: Pernicious anemia  Aplastic Anemia ▪ Temporary or Permanent failure / depression in Bone marrow depression to make enough blood cells (pancytopenia) ▪ Causes: insidious, autoimmune, medications, medical treatments, viruses, and genetic ▪ Onset may be insidious sudden & severe ▪ Manifestations: ▪ Anemia (e.g., weakness, pallor, dyspnea) ▪ Leukocytopenia (e.g., recurrent infections) ▪ Thrombocytopenia (e.g., bleeding) ▪ Diagnosis: complete blood count and bone marrow biopsy ▪ Treatment: identify and manage underlying cause, oxygen therapy, infection control, infection treatment, bleeding precautions, blood transfusions, and bone marrow transplants  Hemolytic Anemia ▪ Excessive erythrocyte destruction ▪ Causes: idiopathic, autoimmune, genetics, infections, blood transfusion reactions, and blood incompatibility in the neonate ▪ Several types including sickle cell anemia, thalassemia, and erythroblastosis fetalis  Sickle Cell Anemia ▪ It is Inherited; neither recessive nor dominant ▪ Result from a defect in the B-chain of the Hb molecule in which a single amino acid (valine) replaces another (glutamic acid) the produced Hb is called HbS. ▪ Hemoglobin S causes erythrocytes to be abnormally shaped. Abnormal erythrocytes carry less oxygen and clog vessels, causing hypoxia and tissue ischemia. ▪ More common in people of African and Mediterranean descent Figure: Sickle cell anemia Forms of Sickle Cell Anemia 1. Sickle cell trait Heterozygous Less than half of erythrocytes are sickled 2. Sickle cell disease Homozygous Most severe Almost all erythrocytes are sickled  Sickle Cell Anemia Manifestations – Typically appear around 4 months of age – Sickle cell crisis Painful episodes that can last for hours to days Pain is caused by tissue ischemia and necrosis Triggered by dehydration, stress, high altitudes, and fever  Sickle Cell Anemia Manifestations Include: abdominal pain, bone pain, dyspnea, delayed growth and development, fatigue, fever, jaundice, pallor, tachycardia, skin ulcers, angina, excessive thirst, frequent urination, priapism, and vision impairment Sickle Cell Disease (cont’d) Table: Complications of Blood Vessel Occlusions in Sickle Cell Anemia  Sickle Cell Anemia Diagnosis: hemoglobin electrophoresis, complete blood count, and bilirubin test Life expectancy improving with better management Treatment: – No cure, palliative – Stem cell research showing promise – Medications (e.g., Hydrea [hydroxyurea]) – Avoid triggers – Other strategies: oxygen therapy, hydration, pain management, infection control, vaccinations, blood transfusions, bone marrow transplants, genetic counseling  Thalassemia Autosomal dominant inheritance Abnormal hemoglobin from a lack of one of two proteins that makes up hemoglobin (alpha and beta globin) Most common in people of Mediterranean descent Manifestations: abortion, delayed growth and development, fatigue, dyspnea, heart failure, hepatomegaly, splenomegaly, bone deformities, jaundice Severe cases can lead to death in childhood Life expectancy can improve with effective management Diagnosis: complete blood count (low MCV, MCHC) and iron levels Treatment: blood transfusion, chelation therapy, and splenectomy  Polycythemia ▪ Abnormally high erythrocytes ▪ Rare ▪ Considered a neoplastic disease ▪ Increased blood volume and viscosity, leading to tissue ischemia and necrosis ▪ Complications: thrombosis, hypertension, heart failure, hemorrhage, splenomegaly, hepatomegaly, and acute myeloblastic leukemia  Polycythemia ▪ Manifestations: cyanotic or plethoric skin, high blood pressure, tachycardia, dyspnea, headaches, visual abnormalities ▪ Diagnosis: complete blood counts, bone marrow biopsy, and uric acid levels ▪ Treatment: chemotherapy, radiation, phlebotomy and managing clotting disorders  Disorder of Platelets ▪ Normal platelet levels range from 150,000 to 350,000 mm3 ▪ Include issues in quantity and quality of platelets ▪ Thrombocytosis – increased levels ▪ Thrombocytopenia – decreased levels  Hemophilia A ▪ X-linked recessive bleeding disorder ▪ Deficiency or abnormality of clotting factor VIII ▪ Varies in severity ▪ Manifestations: bleeding or indications of bleeding (e.g. bruising, petechia, etc) ▪ Diagnosis: clotting studies and serum factor VIII levels ▪ Treatment: clotting factor transfusions, recombinant clotting factors, desmopressin (DDAVP), and bleed precautions  Von Willebrand’s Disease ▪ Most common hereditary bleeding disorder ▪ It results from a deficit of von Willebrand factor, which ordinarily causes platelets to come together (aggregate) and stick (adhere) to the vessel wall in times of injury. ▪ Decreased platelet adhesion and aggregation ▪ Manifestations: bleeding or indications of bleeding (e.g. bruising, petechia, etc) Forms of Von Willebrand’s Disease Type 1 – Most common and mildest form (70-80%) – Autosomal dominant – Reduced von Willebrand’s factor levels – Can cause significant bleeding with trauma or surgery Type 2 – Either autosomal dominant or recessive (15-20%) – Five subtypes – Von Willebrand’s factor building blocks are smaller than usual or break down easily Forms of Von Willebrand’s Disease Type 3 – Autosomal recessive – no measurable von Willebrand’s factor or factor VIII – Causes severe bleeding problems Aquired type – Occurs with Wilms’ tumor, congenital heart disease, systemic lupus erythematosus, and hypothyroidism  Von Willebrand’s Disease Diagnosis: bleeding studies and factor VIII levels Treatment: – Mild cases usually do not require treatment – Cryoprecipitate infusions – Desmopressin (DDAVP) – Bleeding precautions – Measures to control bleeding  Disseminated Intravascular Coagulation (DIC) ▪ Life-threatening complications of many conditions ▪ Results from an inappropriate immune response ▪ Widespread coagulation followed by massive bleeding because of the depletion of clotting factors ▪ Manifestations: tissue ischemia and bleeding ▪ Complications: shock and multisystem organ failure ▪ Diagnosis: complete blood count and bleeding studies ▪ Treatment: identify and treat underlying cause, replace clotting components, and preventing activation of clotting mechanisms Figure: Understanding DIC and its treatment Idiopathic Thrombocytopenia Purpura (ITP) Hypocoagulation resulting from an autoimmune destruction of platelets Acute form – More common in children – Sudden onset – Self-limiting Chronic form – More common in adults age 20-50 – More common in women Causes: idiopathic, autoimmune diseases, immunizations with alive vaccine, immunodeficiency disorders, and viral infections  Idiopathic Thrombocytopenia Purpura Manifestations: bleeding or indications of bleeding (e.g. bruising, petechia, etc) Diagnosis: complete blood count (platelet levels < 20,000) and bleeding studies Treatment: – Acute ITP: glucocorticoid steroids, immunoglobulins, plasmapheresis, and platelet pheresis – Chronic ITP: glucocorticoid steroids, immunoglobulins, splenectomy, blood transfusions, and immunosuppressant therapy Thrombotic Thrombocytopenic Purpura (TTP) ▪ Deficiency of enzyme necessary for cleaving von Willebrand’s factor, leading to hypercoagulation ▪ Hypercoagulation depletes platelet levels ▪ Characterized by thromboses, thrombocytopenia, and bleeding ▪ Causes: idiopathic causes, heredity, bone marrow transplants, cancer, medications, pregnancy, and HIV Thrombotic Thrombocytopenic Purpura ▪ Manifestations: purpura, changes in consciousness, confusion, fatigue, fever, headache, tachycardia, pallor, dyspnea on exertion, speech changes, weakness, and jaundice ▪ Diagnosis: complete blood counts, blood smears, and lactate dehydrogenase levels ▪ Treatment: plasmapheresis, splenectomy, and glucocorticoid steriods