Chapter 11 - Disorders of White Blood Cells and Lymphoid Tissue

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Explain the manifestations of leukemia in terms of altered cell differentiation.

A single progenitor cell undergoes a malignant transformation. This cell will crowd out the marrow, causing proliferation of normal cells to cease.

Describe the following complications of acute leukemia and its treatment: leukostasis, tumor lysis syndrome, hyperuricemia, and blast crisis.

ACUTE LEUKEMIA - Leukostasis: circulating blast count is elevated (100,000uL). This increases blood viscosity which can lead to the development of other complications (leukoblastic emboli) -treatment: use of aphaeresis to remove excess blast cells followed by chemotherapy to stop leukemic cell production in bone marrow ____________________________________________________________ - Hyperuricemia: result of increased proliferation or increased breakdown of purine nucleotides. Prophylactic therapy with allopurinol (drug that inhibits uric acid synthesis) is routinely administered to prevent renal complications. ______________________________________________________________ - Tumor Lysis Syndrome: (TLS) is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer, most commonly after the treatment of lymphomas and leukemias. ___________________________________________________________ - Blast Crisis: the terminal stage of chronic myelogenous leukemia that is characterized by a marked increase in the proportion of blast cells, by fever and pain in the bones, and by increased severity of anemia, thrombocytopenia, and splenomegaly

List the three types of white blood cells and briefly describe their function.

Agranulocytes are divided into 2 different parts: lymphocytes and monocytes/macrophages. Lymphocytes: make up 30% of leukocytes. They originate in bone marrow and migrate through peripheral lymphoid organs where they recognize antigens and participate in immune responses. Monocytes/macrophages: make up 3-8% of leukocytes. They travel from bone marrow to body tissue where they differentiate into various phagocytes.

Contrast and compare the signs and symptoms of Hodgkin lymphoma and non-Hodgkin lymphoma

Although the diseases may sound similar, there is a lot of difference between Hodgkin and non-Hodgkin lymphoma. Both Hodgkin and non-Hodgkin lymphoma are malignancies of a family of white blood cells known as lymphocytes, which help the body fight off infections and other diseases. Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells, which are mature B cells that have become malignant, are unusually large, and carry more than one nucleus. The first sign of the disease is often the appearance of enlarged lymph nodes. Non-Hodgkin lymphoma, by contrast, can be derived from B cells or T cells and can arise in the lymph nodes as well as other organs. (B cells and T cells play different roles in the body's immune response to disease.) Both diseases are relatively rare, but non-Hodgkin lymphoma is more common in the United States, with more than 70,000 new cases diagnosed each year, compared to about 8,000 for Hodgkin lymphoma. The median age of patients with non-Hodgkin lymphoma is 60, but it occurs in all age groups. Hodgkin lymphoma most often occurs in people ages 15 to 24 and in people over 60. There are more than 60 distinct types of non-Hodgkin lymphoma, whereas Hodgkin lymphoma is a more homogeneous disease. The two forms of lymphoma are marked by a painless swelling of the lymph nodes. Hodgkin lymphomas are more likely to arise in the upper portion of the body (the neck, underarms, or chest). Non-Hodgkin lymphoma can arise in lymph nodes throughout the body, but can also arise in normal organs. Patients with either type can have symptoms such as weight loss, fevers, and night sweats. The diseases often follow different courses of progression. Hodgkin lymphoma tends to progress in an orderly fashion, moving from one group of lymph nodes to the next, and is often diagnosed before it reaches an advanced stage. Most patients with non-Hodgkin lymphoma are diagnosed at a more advanced stage. Treatments for lymphoma vary depending on the type of disease, its aggressiveness, and location, along with the age and general health of the patient. As a general rule, however, Hodgkin lymphoma is considered one of the most treatable cancers, with more than 90 percent of patients surviving more than five years. Survival rates for patients with non-Hodgkin lymphoma tend to be lower, but for certain types of the disease, the survival rates are similar to those of patients with Hodgkin lymphoma. New treatment approaches, including the use of therapies that spur the immune system to attack cancerous lymphocytes, are showing considerable promise.

Describe the treatment measures used in Hodgkin disease and non-Hodgkin lymphoma.

Chemotherapy Chemotherapy is a drug treatment that uses chemicals to kill lymphoma cells. Chemotherapy drugs travel through your bloodstream and can reach nearly all areas of your body. Chemotherapy is often combined with radiation therapy in people with early-stage classical type Hodgkin's lymphoma. Radiation therapy is typically done after chemotherapy. In advanced Hodgkin's lymphoma, chemotherapy may be used alone or combined with radiation therapy. Chemotherapy drugs can be taken in pill form or through a vein in your arm, or sometimes both methods of administration are used. Several combinations of chemotherapy drugs are used to treat Hodgkin's lymphoma. Side effects of chemotherapy depend on the drugs you're given. Common side effects are nausea and hair loss. Serious long-term complications can occur, such as heart damage, lung damage, fertility problems and other cancers, such as leukemia. Radiation therapy Radiation therapy uses high-energy beams, such as X-rays and protons, to kill cancer cells. For classical Hodgkin's lymphoma, radiation therapy is often used after chemotherapy. People with early-stage nodular lymphocyte-predominant Hodgkin's lymphoma may undergo radiation therapy alone. During radiation therapy, you lie on a table and a large machine moves around you, directing the energy beams to specific points on your body. Radiation can be aimed at affected lymph nodes and the nearby area of nodes where the disease might progress. The length of radiation treatment varies, depending on the stage of the disease. A typical treatment plan might have you going to the hospital or clinic five days a week for several weeks. At each visit, you undergo a 30-minute radiation treatment. Radiation therapy can cause skin redness and hair loss at the site where the radiation is aimed. Many people experience fatigue during radiation therapy. More-serious risks include heart disease, stroke, thyroid problems, infertility and other cancers, such as breast or lung cancer. Bone marrow transplant Bone marrow transplant, also known as stem cell transplant, is a treatment to replace your diseased bone marrow with healthy stem cells that help you grow new bone marrow. A bone marrow transplant may be an option if Hodgkin's lymphoma returns despite treatment. During a bone marrow transplant, your own blood stem cells are removed, frozen and stored for later use. Next you receive high-dose chemotherapy and radiation therapy to destroy cancerous cells in your body. Finally your stem cells are thawed and injected into your body through your veins. The stem cells help build healthy bone marrow. People who undergo bone marrow transplant may be at increased risk of infection. Other drug therapy Other drugs used to treat Hodgkin's lymphoma include targeted drugs that focus on specific vulnerabilities in your cancer cells and immunotherapy that works to activate your own immune system to kill the lymphoma cells. If other treatments haven't helped or if your Hodgkin's lymphoma returns, your lymphoma cells may be analyzed in a laboratory to look for genetic mutations. Your doctor may recommend treatment with a drug that targets the particular mutations present in your lymphoma cells. Targeted therapy is an active area of cancer research. New targeted therapy drugs are being studied in clinical trials.

Use the concepts regarding the central and peripheral lymphoid tissues to describe the site of origin of the malignant lymphomas, leukemias, and plasma cell dyscrasias.

Lymphocytic leukemias: Immature lymphocytes and their progenitors that infiltrate the spleen, lymph nodes, CNS, and other tissues. Myelogenous leukemias Involve the pluripotent myeloid stem cells in bone marrow- interfere with the maturation of all blood cells, including the granulocytes, erythrocytes, and thrombocytes. Plasma cell dyscrasias:

Describe the mechanism of symptom production in neutropenia

Mild to moderate: skin lesions,stomatits, pharyngitis, diarrhea severe: malaise, chills, fever, fatigue, weakness very severe: none

Define infectious mononucleosis and describe the pathogenesis, clinical manifestations, and treatment.

Mononucleosis is an infectious illness that's sometimes called mono or "the kissing disease." While you can get the virus that causes it through kissing, you can also get it in other ways like sharing drinks or utensils. It's contagious, but you're less likely to catch mono than other illnesses like the common cold. In general, the Epstein-Barr virus (EBV) is what causes mono. It's a common virus that many people are exposed to as kids. But even if you're exposed to EBV, it's not guaranteed that you'll get mono. It's possible to be infected with EBV and carry it in your body for your entire life without ever having symptoms of mono. through saliva, which is why you can get it from kissing. You can also get it if you share food, drinks, or silverware with a person who has it, or if an infected person coughs or sneezes near you. As long as an object -- like a fork or spoon -- that an infected person used is still moist, the virus is probably still present and contagious. There's no vaccine to prevent mono. EBV can stay in your saliva for months after you're infected, so even if you don't have symptoms or feel sick, you may be able to spread it. This makes it hard to prevent the spread of mono. To lower your chance of getting it, wash your hands often and try not to share such things as drinks or silverware with other people.

Cite two general causes of neutropenia.

Neutrophils are produced in the bone marrow at the center of larger bones. Anything that disrupts this process can cause neutropenia. Most commonly, neutropenia is caused by chemotherapy for cancer. In fact, around half of cancer patients undergoing chemotherapy will experience some level of neutropenia. Other potential causes of neutropenia include: leukemia certain medications, including antibiotics and drugs for high blood pressure, psychiatric disorders, and epilepsy. Barth syndrome, a genetic disorder affecting multiple systems myelodysplastic syndromes, which are a group of disorders characterized by dysfunctional blood cells due to problems with bone marrow production myelofibrosis, a rare bone marrow problem, also known as osteomyelofibrosis alcohol dependency vitamin deficiencies, most commonly vitamin B12, folate, and copper deficiency. sepsis, an infection of the bloodstream that uses up neutrophils quicker than they can be produced. Pearson syndrome certain infections, including hepatitis A, B, and C, HIV/AIDS, malaria, tuberculosis, dengue fever, and Lyme disease. hypersplenism, or an enlarged spleen Some autoimmune conditions can target neutrophils, reducing their number. These conditions include: Crohn's disease rheumatoid arthritis lupus

List the three subtypes of granulocytes and briefly describe their role.

Neutrophils: make up 60-65% of leukocytes. They maintain normal host defenses against invading bacteria and fungi cell debris, and a variety of foreign substances. Eosinophils: make up 1-3% of leukocytes. They are a part of 2 reactions. Allergic reactions: they release enzymes or chemical mediators that detoxify agents associated with the reaction. Parasitic infections: Basophils: make up .3-.5% of leukocytes. They contain heparin, an anticoagulant; and histamine, a vasodilator, and other mediators of inflammation.

trace the development of the different blood cells from their origin in the pluripotent bone marrow stem cell to their circulation in the bloodstream.

The Pluripotent stem cell gives rise to the lymphoid stem cell and the myeloid stem cell. These both differentiate into different cells. The Lymphoid stem cell differentiates into T cells, B cells, and natural killer (NK) cells. B cells turn into plasma cells. Meanwhile, myeloid stem cells differentiate into monocytes, granulocytes, megakaryocytes, and erythrocytes. Monocytes turn into monoblasts. Granulocytes turn into eosinophils, neutrophils, and basophils. Megakaryocytes turn into platelets. Erythrocytes turn into reticulocytes. This is what circulates in the blood stream.

List the cells and tissues of the hematopoietic system.

The hematopoietic system consists of organs and tissues, primarily the bone marrow, spleen, tonsils, and lymph nodes involved in the production of blood. Blood is composed of the liquid component of plasma, and the solid components, which are mainly erythrocytes, leukocytes, and thrombocytes.

11. Use the predominant white blood cell type and classification of acute or chronic to describe the four general types of leukemia.

There are several different types of leukemia. In general, leukemia is grouped by how fast it gets worse and what kind of white blood cell it affects. It may be acute or chronic. Acute leukemia gets worse very fast and may make you feel sick right away. Chronic leukemia gets worse slowly and may not cause symptoms for years. It may be lymphocytic or myelogenous. Lymphocytic (or lymphoblastic) leukemia affects white blood cells called lymphocytes. Myelogenous leukemia affects white blood cells called myelocytes. The four main types of leukemia are: • Acute lymphocytic leukemia, or ALL. Acute lymphocytic leukemia occurs when a bone marrow cell develops errors in its DNA. The errors tell the cell to continue growing and dividing, when a healthy cell would normally stop dividing and die. When this happens, blood cell production becomes abnormal. The bone marrow produces immature cells that develop into leukemic white blood cells called lymphoblasts. These abnormal cells are unable to function properly, and they can build up and crowd out healthy cells. It's not clear what causes the DNA mutations that can lead to acute lymphocytic leukemia. But doctors have found that most cases of acute lymphocytic leukemia aren't inherited. Acute lymphocytic leukemia is the most common type of cancer in children, and treatments result in a good chance for a cure. Acute lymphocytic leukemia can also occur in adults, though the chance of a cure is greatly reduced. • Acute myelogenous leukemia, or AML. Acute myelogenous leukemia is caused by damage to the DNA of developing cells in your bone marrow. When this happens, blood cell production goes awry. The bone marrow produces immature cells that develop into leukemic white blood cells called myeloblasts. These abnormal cells are unable to function properly, and they can build up and crowd out healthy cells. In most cases, it's not clear what causes the DNA mutations that lead to leukemia. Radiation, exposure to certain chemicals and some chemotherapy drugs are known risk factors for acute myelogenous leukemia. • Chronic lymphocytic leukemia, or CLL. Doctors are unsure as to the exact cause of CLL. But they do know that something happens in order to cause a genetic mutation in the DNA of blood-producing cells. This mutation causes the blood cells to produce abnormal, ineffective lymphocytes — one type of white blood cell that helps your body fight infection. Beyond being ineffective, these abnormal lymphocytes continue to live and multiply, when normal lymphocytes would die. The abnormal lymphocytes accumulate in the blood and certain organs, where they cause complications. They may crowd healthy cells out of the bone marrow and interfere with normal blood cell production. • Chronic myelogenous leukemia, or CML. Chronic myelogenous leukemia typically affects older adults and rarely occurs in children, though it can occur at any age. Your blood cells originate in the bone marrow, a spongy material inside your bones. When your bone marrow functions normally, it produces immature cells (blood stem cells) in a controlled way. These cells then mature and specialize into the various types of blood cells that circulate in your body — red cells, white cells and platelets. In chronic myelogenous leukemia, this process doesn't work properly. The tyrosine kinase caused by the BCR-ABL gene causes too many white blood cells. Most or all of these contain an abnormal chromosome called the Philadelphia chromosome. The diseased white blood cells don't grow and die like normal cells. The diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.

Define the terms leukopenia, neutropenia, granulocytopenia, and aplastic anemia.

leukopenia: decrease in absolute number of leukocytes in blood neutropenia: abnormally low number of neutrophils with circulating count less than 1500/uL granulocytopenia: aplastic anemia: when all myeloid stem cells are affected causing anemia, thrombocytopenia, and agranulocytosis

Describe the role of the lymphoid tissues.

lymphocyte production for immune response. Lymphoid tissue makes up the lymph nodes, thymus, spleen, and bone marrow. In the lymph nodes, lymphoid tissue makes up fibrous capsules and radiating trabeculae which provides a supporting structure, and a delicate reticular network contributes to internal support.


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