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Alterations of Erythrocyte Function
- Anemia is generally defined as a reduction in the number of volume of circulating red cells or an alteration in hemoglobin.
- The most common classification of anemias is based on changes in the cell size – represented by the suffix cytic – and changes in the cell’s hemoglobin content – represented by the suffix chromic.
- Clinical manifestations of anemia can be found in all organs and tissues throughout the body. Decreased oxygen delivery to tissues causes fatigue, dyspnea, syncope, angina, compensatory tachycardia, and organ dysfunction.
- Macrocytic (megaloblastic) anemias are caused most commonly by deficiency of vitamin B12. Pernicious anemia can be fatal unless vitamin B12 replacement is given.
- Microcytic-hypochromic anemias are characterized by abnormally small red cells with insufficient hemoglobin content. The most common cause is iron deficiency.
- Iron deficiency anemia usually develops slowly, with a gradual insidious onset of symptoms, including fatigue, weakness, dyspnea, alteration of various epithelial tissues, and vague neuromuscular complaints.
- Iron deficiency anemia is usually a result of a chronic blood loss or decreased iron intake. Once the source of blood loss is identified and corrected, iron replacement therapy can be initiated.
- Sideroblastic anemia results from impaired iron metabolism and abnormal sequestration of iron within the red cell. Treatment varies depending on the cause.
- Normocytic-normochromic anemias are characterized by insufficient numbers of normal erythrocytes. Included in this category are aplastic, posthemorrhagic, and hemolytic anemia and anemia of chronic inflammation.
- In aplastic anemia, erythrocyte stem cells are underdeveloped, defective or absent. Unless the cause is determined, bone marrow aplasia results in death.
- Posthemorrhagic anemia results from a sudden blood loss. Restoration of blood volume by plasma expanders or transfusions may diminish subjective symptoms of anemia. Hemoglobin restoration may take 6 to 8 weeks.
- Hemolytic anemia results from premature destruction of red cells and may be acquired or hereditary. Of the acquired forms, autoimmune reaction and drug induced hemolysis are the most common causes.
- Anemia of chronic inflammation is associated with chronic infections, chronic inflammatory diseases, and malignancies.
Myeloproliferative Red Cell Disorders
- Polycythemia vera is characterized by excessive proliferation of erythrocyte precursors in the bone marrow. Signs and symptoms result directly from increased blood volume and viscosity. Therapeutic phlebotomy to remove excessive blood volume and use of radioactive phosphorus have been helpful in decreasing the excessive red cell pool.
- Polycythemia vera may spontaneously covert to acute myelogenous leukemia.
Alterations of Leukocyte Function
- Quantitative alterations of leukocytes (too many or too few) can be caused by bone marrow dysfunction or premature destruction of cells in the circulation. Many quantitative changes in leukocytes occur in response to invasion by microorganisms.
- Leukocytosis is a condition in which the leukocyte count is higher than normal and is usually a response to stress and invasion of microorganisms.
- Leukopenia is a condition in which the leukocyte count is lower than normal and is caused by pathologic conditions, such as malignancies and hematologic disorders.
- Granulocytosis (particularly as a result of an increase in neutrophils) occurs in response to infection. The marrow releases immature cells, causing a shift-to-the-left, when responding to an infection that has created a demand for neutrophils that exceeds the supply in the circulation.
- Eosinophilia results most commonly from parasitic invasion and ingestion or inhalation of toxic foreign particles.
- Basophilia is seen in hypersensitivity reactions because of the high content of histamine and subsequent release.
- Monocytosis occurs during the late or recuperative phase of infection when macrophages (mature monocytes) phagocytose surviving microorganisms and debris.
- Granulocytopenia, a significant decrease in neutrophils, can be a life-threatening condition if sepsis occurs; it is often caused by chemotherapeutic agents, severe infection, and radiation.
- Infectious mononucleosis is an acute infection of B lymphocytes most commonly associated with the Epstein-Barr virus (EBV), a type of herpes virus. Transmission of EBV is through close personal contact, commonly through saliva, thus its nickname, the kissing disease.
- Two of the earliest manifestations of infectious mononucleosis are sore throat and fever caused by inflammation at the primary site of viral entry.
- Most causes of EBV infectious mononucleosis include fever lasting 7 to 10 days, sore throat, and enlargement and tenderness of the cervical lymph nodes, it is self-limiting and treatment consists of rest and symptomatic treatment.
- The common pathologic feature of all forms of leukemia is an uncontrolled proliferation of leukocytes, overcrowding the bone marrow and resulting in decreased production and function of the other blood cell lines.
- All leukemias are classified by the cell type involved, (a) lymphocytic or (b) myelogenous, and are differentiated by onset, acute, or chronic. Thus, there are four major types of leukemia: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML).
- Although the exact cause of leukemia is unknown, it is considered a clonal disorder. A high incidence of acute leukemias and CLL is reported in certain families, suggesting a genetic predisposition.
- The major clinical manifestation of leukemia includes fatigue caused by anemia, bleeding caused by thrombocytopenia, fever secondary to infection, anorexia, and weight loss.
- Chemotherapy is the treatment of choice for leukemia. Acute leukemias are associated with an increasing survival rate of 80% to 90%, with long-term survival of 30% to 40%. Chronic leukemias are associated with a longer life expectancy than are acute leukemias.
- Chronic leukemias progress differently than acute leukemias, advancing slowly and without warning. The presence of the Philadelphia chromosome is a diagnostic marker for CML.
Alterations of Lymphoid Function
- The number of lymphocytes is decreased (lymphocytopenia) in most acute infections and in some immunodeficiency syndromes.
- Lymphocytosis occurs in viral infections (infectious mononucleosis and infectious hepatitis, in particular), leukemia, lymphomas, and some chronic infections.
- Lymphomas are tumors of primary lymphoid tissue (thymus, bone marrow) or secondary lymphoid tissue (lymph nodes, spleen, tonsils, intestinal lymphoid tissue). The two major types of malignant lymphomas are Hodgkin lymphoma and non-Hodgkin lymphoma.
- Distinctive abnormal chromosomes are present in multiple cells of the lymph nodes of an individual with Hodgkin lymphoma. The abnormal cell is celled the Reed-Sternberg cell.
- A virus might be involved in the pathogenesis of Hodgkin lymphoma. Some familial clustering suggests an unknown genetic mechanism.
- An enlarged, painless mass or swelling, most commonly in the neck, is an initial sign of Hodgkin lymphoma. Local symptoms are produced by lymphadenopathy, usually caused by pressure or obstruction.
- Treatment of Hodkin lymphoma includes radiation therapy and chemotherapy. A cure is possible regardless of the stage of Hodgkin lymphoma; however, individuals treated with chemotherapy who relapse in less than 2 years have a poor prognosis.
- The cause of lymph node enlargement and cancerous transformation in non-Hodgkin lymphoma is unknown. Immunosuppressed persons have a higher incidence of non-Hodgkin lymphoma, suggesting an immune mechanism.
- Generally, with non-Hodgkin lymphoma, the swelling of lymph nodes is painless, and the nodes enlarge and transform over a period of months or years.
- Individuals with non-Hodgkin lymphoma can survive for long periods. The treatment used is chemotherapy.
- Burkitt lymphoma involves the jaw and facial bones and occurs in children from east-central Africa and New Guinea.
- Multiple myeloma is a neoplasm of B cells (immature plasma cells) and mature plasma cells. It is characterized by multiple malignant tumor masses of plasma cells scattered throughout the skeletal system and sometimes found in soft tissue.
- The exact cause of multiple myeloma is unknown, but genetic factors and chronic stimulation of the mononuclear phagocyte system by bacteria, viral agents, and chemicals have been suggested.
- The major clinical manifestations for multiple myeloma include recurrent infections caused by suppression of the humoral immune response and renal disease as a result of Bence Jones proteinuria.
- Chemotherapy is the treatment of choice for multiple myeloma. Survival is still only 2 to 3 years with chemotherapy, however. Treatment with thalidomide is showing promise as an effective therapeutic agent in producing long-term remissions.
Alterations of Splenic Function
- Splenomegaly (enlargement of the spleen) may be considered normal in certain individuals, but its presence should not be ignored.
- Splenomegaly results from (a) acute inflammatory or infectious processes, (b) congestive disorders, (c) infiltrative processes, and (d) tumors or cysts.
- Hypersplenism (overactivity of the spleen) results from splenomegaly. Hypersplenism results in sequestering of the blood cells, causing increased destruction of red blood cells, which leads to the development of anemia.
Alterations of Platelets and Coagulation
- Thrombocytopenia is characterized by a platelet count below 100,000/mm3 of blood; a count below 50,000/mm3 increases the potential for hemorrhage associated with minor trauma.
- Thrombocytopenia exists in primary or secondary forms and is commonly associated with autoimmune diseases and viral infections; bacterial sepsis with DIC also results in thrombocytopenia.
- Thrombocytopenia is characterized by a platelet count more than 400,000 platelets/mm3 of blood and is symptomatic when the count exceeds 1,000,000/mm3, at which time the risk for intravascular clotting (thrombosis) is high.
- Thrombocytopenia is cause by accelerated platelet production in the bone marrow.
- Qualitative alterations in normal platelet adherence or aggregation prevent platelet plug formation and may result in prolonged bleeding times.
- Platelet dysfunction results from changes in the cellular contents and integrity.
- Disorders of coagulation are usually caused by defects or deficiencies of one or more clotting factors.
- Coagulation is impaired when there is a deficiency of vitamin K because of insufficient production of prothrombin and synthesis of clotting factors II, VII, Ix, and I, often associated with liver diseases.
- Disseminated intravascular coagulation (DIC) is a complex syndrome resulting from a variety of clinical conditions that release tissue factor causing an increase in fibrin and thrombin activity in the blood producing augmented clot formation and accelerated fibrinolysis. Sepsis is a condition that is often associated with DIC.
- DIC is characterized by a cycle of intravascular clotting followed by active bleeding caused by the initial consumption of coagulation factors and platelets and diffuse fibrinolysis.
- Diagnosis of DIC is based on measurement in the blood of end products characteristic of dysfunctional coagulation activity. Treatment is complex and non-standardized and focused on removing the primary cause, restoring hemostasis, and preventing further organ damage.
- Thromboembolic disease results from a fixed (thrombus) or moving (embolus) clot that blocks flow within a vessel, denying nutrients to tissues distal to the flow to the heart, brain, or lungs.
- Hypercoagulability is the result of deficient anticoagulation proteins. Secondary causes are conditions that promote venous stasis.
- The term Virchow triad refers to three factors that can cause thrombus formation: (a) loss of integrity of the vessel wall, (b) abnormalities of blood flow, and (c) alterations in the blood constituents.