Chapter 11 - Disorders Of WBC And Lymphoid Tissues Flashcards
What is the bone marrow and hematopoiesis? What are the three types of cells? What are the hematopoietic growth factors?
Consists of hematopoietic or blood forming cells and stromatolites tissue that provides support for the blood forming cells. There are three types of cells; pluripotent stem cells, multipotent stem cells, and committed progenitor cells that develop into the various types of blood cells. Pluripotent stem cells give rise to two types of multi potential stem cells, the common lymphoid and the common myeloid stem cells. The common lymphoid stem cells in turn differentiate into lineage specific precursor cells that develop into T lymphocytes (T cells, B lymphocytes, and natural killer cells. From the common myeloid stem cells arise precursor cells capable of differentiating along the erythrocytes/megakaryocytic and granulocyte monocytes pathways.
The number and total mass for each type of circulating blood cell remain relatively constant. Is thought to be at least partially controlled by hormone like growth factors called cytokines. They are a family of short lived mediators that stimulate the proliferation, differentiation and functional activation of various blood cells. Colony stimulating factor CSF that act on committed progenitor cells include erythropoietin, thrombopoietin, granulocyte monocytes CSF, which stimulates progenitors for granulocytes, monocytes, erythrocytes, and megakaryocytes; granulocyte CSF which promotes the proliferation of neutrophils; and macrophage CSF induces macrophage colonies. Interleukins, interferons, and tumor necrosis factor support the proliferation of stem cells and the development of lymphocytes and act synergistically to aid the multiple functions of CSF. Clinically these factors are used for treatment of bone marrow failure by chemotherapy or aplastic anemia, the anemia of kidney failure and cancer, hematopoietic neoplasms, infectious diseases AIDS and congenital and myeloproliferative disorders.
What are the two classes of leukocytes? What are the leukocytes for each class? What are the leukocyte developmental stages?
- Granulocytes - neutrophils, eosinophils, basophils - they are spherical and have distinctive multipolar nuclei. They are all phagocytosis cells that’s are identifiable because of their cytoplasmic granules. There are three granulocytes
1.neutrophils - which constitute 60-65% of total WBC have specific granules that are neutral and dont stain with acidic or basic dye. Because they have nuclei that’s are divided into three to five lobes they are often called polymorphonuclear leukocytes. They are Romario responsible for maintaining normal host defended against invading bacteria and fungi, cell debris and a variety of foreign substances. After release from the marrow, they spend only approx. 4-8 hrs in the circulation before moving into the tissues where they survive for 4-5 days. They die in the tissues by discharging their phagocytosis function or from senescence. These respond to chemotactic factors and migrate into the tissues toward the offending agent during an inflammatory reactions. - Eosinophils - stain red with the acidic dye eosin. They constitute 1-3% of the total WBC and increase in number during allergic reactions and parasitic infections. They are thought to release enzymes or chemical mediator that’s detoxify agents associated with the reaction. In parasitic infections they use surface markers to attach themselves to the parasite and then releases hydrolytic enzymes that kill it.
- Basophils are the least numerous and account for .3-.5%. They stain blue with a basic dye. They contain heparin, an anticoagulant; histamine, a vasodilator; and other mediators of inflammation. Is related to the connective tissue mast cell, they are both thought to be involved in allergic and hypersensitivity reactions
Agranulocytes that lack cytoplasmic granules - Lymphocytes - are the most common, account for 30% of total blood leukocytes. They originate in the bone marrow from lymphoid stem cells and migrate through the peripheral lymphoid organs, where they recognize antigens and participate in the immune responses. 3 types B cells, T cells, and natural killer cells. B cells differentiate to form antibody producing plasma cells and are involved in humoral mediated immunity. T cells differentiate in the thymus, they activate other cells of the immune system and are involved in cell mediated immunity. NK cells participate in innate or natural immunity and their function is to destroy foreign cells. They all have unique surface markers that can be identified and used to define their function and diagnose disease. They comprise elements that vary in terms of lineage, cell membrane molecules and receptors, function and response to antigen. Are often distinguished by surface proteins that can be identified using panels of monoclonal antibodies.
- Monocytes/macrophages - are the largest of WBC and are 3-8% of total leukocyte count. They are distinguished by a large amount of cytoplasm and a darkly stained kidney shaped nucleus. They contain small, dense, azurophilic granules that contain lysosomal enzymes similar to those found in granules of neutrophils. They travel from bone marrow to the body tissues, where they differentiate into various tissue phagocytes including histiocytes of loose connective tissue, microglial cells of the brain, Kupffer cells of the liver, and tissue macrophages. During inflammation, they leave the blood vessel at the site of inflammation and transform into tissue macrophages that phagocytosis bacteria and tissue debris. They also play an important role in immune responses by activating lymphocytes and by presenting antigen to T cells.
They begin with myeloid and lymphoid stem cells in the bone marrow. The immature precursor cells for each of the cell lines are called blast cells. P 245 fig 11-3. The granulocytic precursor cells, which are called myeloblasts, have round to oval nuclei, with delicate chromatin and a blue to gray cytoplasm. The myeloblasts are transformed into promyelocytes with similar nuclei but with cytoplasm containing many primary granules.
What are lymphoid tissues?
Consists of the lymphatic vessels, lymphoid tissue and lymph nodes, thymus and spleen. B and T cells begin in the bone marrow then they migrate to these structures. Lymph nodes consist of organized collection of lymphoid tissue located along the lymphatic vessels. Typically greyish white and ovoid or bean shaped, they range in diameter from 1 mm to 1-2 cm. A fibrous capsule and radiating trabeculae provide a supporting structure, a delicate reticular network contributes to internal support. It is divided into outer cortex and an inner medulla. Cortex contains well defined b and T cell domains. The superficial outer cortex contains aggregates of Elle called follicles. They are B cell zones of the lymph nodes. There are two types; immunologically inactive follicles are called primary, and active follicles that contain terminal centres called secondary follicles. Germinal centres contain large lymphocytes centroblasts and small lymphocytes with cleaved nuclei centroytes. The mantle zone is the small layer of B cells surrounding the germinal centres. The cortex around the follicles is called the paracortex. And contains the most T cells in the lymph nodes.
The alimentary canal, respiratory passages, and genitourinary systems are guarded by accumulations of lymphoid tissue that are not enclosed in a capsule mucosa associated lymphoid tissue MALT
What is nonneoplastic disorders of WBC? What is neutropenia (agranulocytosis)?
Leukocytes WBC in the circulation normally ranges from 4500 - 10500 cells. These disorders of WBC include a deficiency of leukocytes or proliferation of excess WBC. Leukopenia describes a dec in number of leukocytes in the blood. It may affect any of the specific types of WBC but most often neutrophils. In aplastic anemia, all myeloid stem cells are affected, anemia, thrombocytopenia, agranulocytosis.
It refers specifically to an abnormally low number of neutrophils and is commonly defined as count less then 1500. Mild 1000-1500, moderate 500-1000 or severe <500. Since it protects against bacterial infections, persons with neutropenia are prone to recurrent and sometimes severe bacterial infections. Some African descent and other ethnic groups from the Middle East have lower neutrophil counts without predisposition to bacterial infection, benign ethnic neutropenia.
Pathogenesis - Can be seen in wide variety of conditions, neoplasms, autoimmune disorders, and drug effect. And a group of rare inherited disorders such as Kostmann syndrome.
Congenital neutropenia - a dec production of granuloctyes is a feature of a group of hereditary hematologic disorders. It is an autosomal dominant disorder with variable expression that begins in infancy and persists for decades. It develops every 21 days and lasts approx. 2-3 days. Treatment - includes the administration of G CSF before this therapy was developed almost all pt died in childhood.
Acquired neutropenia - aplastic anemia and treatment with cancer chemo drugs and irradiation may cause suppression of bone marrow stem cells. Overgrowth of neoplasticism cells in cases of nonmyelogenous leukaemia and lymphoma also may suppress the function of neutrophil precursors. In splenomegaly, they may be trapped in the spleen along with other blood cells. Autoimmune disorders or idiosyncratic drug reaction may cause inc and premature destruction of neutrophils. In felty syndrome, a variant of rheumatoid arthritis there is a inc destruction of neutrophils in the spleen. Infection by viruses or bacteria may drain neutrophils from the blood faster than they can be replaced, thereby depleting the neutrophil storage pool in the bone marrow. Many are drug related. Idiosyncratic is used to describe drug reactions that are different from the effects observed in most persons and that cant be explained in terms of allergy. Chloramphenicol (antibiotic) phenothiazines (antipsychotic) propylthiouracil (hyperthyroidism) phenyl it’s one (arthritis) may cause depression of bone marrow function.
Clinical course - usually depend on the cause and severity of the disorder. From any cause places pt at risk for infection by gram positive and gram negative bacteria and by fungi. The risk of infection is related to the severity of the neutropenia. Pt with chronic benign are often free of infection despite low counts. They provide the first line of defence against organisms that inhabit the skin and GI tract. Skin infections and ulcerative necrotizing lesions of the mouth are common types of infection. The most frequent important site is the respiratory tract. Untreated infections can be rapidly fatal, especially if the count is below 250.
Treatment is with antibiotics and G CSF can by used to stimulate the maturation and differentiation of granulocytic line.
What’s is infectious mononucleosis?
It is a self-limiting lymphoproliferative disorder caused by the Epstein Barr virus EBV, a member of the herpesvirus family. It may occur at any age, but usually in adolescents and young adults in develops countries. It is one of the viruses that is most successful in evading the immune syste, infecting about 90% of humans and persisting for the lifetime of the person. It spreads from person to person primarily through contact with infected oral secretions. Requires close contact.
Pathogenesis - is largely transmitted through oral contact withEBV contaminated saliva. The virus initially penetrates the nasopharyngeal, oropharyngeal and salivary epithelial cells. It then spreads to underlying oropharyngeal lymphoid and to B cells all of which have receptors for EBV. It may kill off the B cell or it may incorporate itself into the cell’s genome. They then proliferate in the circulation and produce the well known heterophil antibodies that are used for diagnosis. It is a immunoglobulin that react with antigens from another species. After recovery a few transformed B cells in the oropharyngeal region and is she in the saliva. Once infected with the virus, your infected for life and may continue to shed EBV.
Clinical course - is insidious, incubation period from time of initial exposure to onset of symptoms is estimated at 4-8 weeks. A pro formal period which lasts for several days follows and is characterized by malaise, anorexia, and chills. Then fever, pharyngitis, and lymphadenopathy. Sore throat is most severe on days 5-7 and last for 7-14 days. The lymph nodes are typically enlarge throughout the body. Hepatitis and splenomegaly are common manifestations. First - may have nausea, anorexia, hepatomegaly and jaundice but usually is a benign condition. Spleen may enlarge two - three times its normal size, and rupture of the spleen is an infrequent complication. <15 have CNS complications include cranial nerve palsies, encephalitis meningitis, transfers myelitis, and Guillain Barre Syndrome. The peripheral blood usually shows an inc in the number of leukocytes with wBC 12000-18000. The acute phase is urually 2-4 wks, some degree of debility and lethargy . Treatment is primarily symptomatic and supportive. Includes bed rest and analgesics Tylenol and notsteroidal anti inflammaatory NSAIDs to relieve fever, headache and sore throat. If splenic rupture is rate, avoidance of contact sports for a min of 3 wks.
What are neoplasticism disorders of hematopoietic and lymphoid origin? What are leukemias?
They represent the most important of the WBC disorders. They can be divided into tow broad categories based on the origin of the tumor cells; lymphoid neoplasms and myeloid neoplasms. The clinical features are largely determined by their site of origin, the progenitor cell from which they originated, and the molecular events involved in their transformation into a malignant neoplasm.
Leukemias are malignant neoplasms of cells originally derived from precursor myeloid or lymphoid tissue cells. Because blood cells circulate throughout the body, these neoplasms are often disseminated from the onset. They may infiltrate the liver, spleen, lymph nodes and other tissues throughout the body.
Classification - are commonly classified according to their predominant cell type and whether the condition is acute or chronic. Biphenotypic leukemias demonstrate characteristics of both lymphoid and myeloid lineages. The lymphocytic leukemias involve immature lymphocytes and their progenitors that originate in the bone marrow but infiltrate the spleen, lymph nodes, CNS and other tissues. The myelogenous leukemias, which involve the pluripotent myeloid stem cells in bone marrow, interfere with the maturation of all blood cells, including granulocytes , erythrocytes and thrombocytes. 4 types Acute lymphocytes leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML) and chronic myelocytic leukemia (CML). ALL is most common in children and adolescents 75% of leukemia cases. OLder adults 20 and up usually have CLL 38% and AML 30 %.
Etiology and molecular biology - Causes are largely unknown some ionizing radiation has been from other cancers treatments. Family history shows a link with CLL. The biology suggest that’s the event or events causing the disorders exert their effects through disruption or dye regulation of genes that normally regulate blood cell development, blood cell homeostasis or both. So translocations or inversion and deletions. It appears to that leukemia results at least in part from disruption in the activity of genes that normally regulate blood cell development.
What is acute leukemias? What are the two main forms?
Are cancers of the hematopoietic progenitor cells, usually have a sudden and stormy onset with sing related to depressed bone marrow function. Two main acute lymphocytic leukemia (ALL) and acute myeloid leukemia AML. Most cases of ALL are of pre B cell origin. Approx. 90% of ALL have numeric and structural changes in the chromosomes of their leukemia cells.. AML are a diverse group of neoplasms affecting myeloid precursor cells in bone marrow. Most with acquired genetic alteration that inhibit terminal myeloid differentiation. As a result, normal marrow elements are replaced by a n accumulation of relatively undifferentiated blast cells, the result is suppression of the remaining progenitor Elle and subsequent anemia, neutropenia, a thrombocytopenia.
Manifestation - they typically present with similar clinically features. By an abrupt onset of symptoms, including fatigue resulting from anemia; low grade fever, night sweats, and weight loss due to the rapid proliferation and hyper metabolism of the leukemic cells; bleeding due to a dec in platelet count; and bone pain and tenderness due to bone marrow expansion. Infection results from neutropenia with the risk of infection rising steeply as the neutropenia count falls below 500. Generalized lymphadenopathy, splenomegaly, and hepataomegaly caused by infiltrate ion of leukemic cells occurs. AML usually has infiltrataion of malignant cells in the skin, gums, and other soft tissues with monocytes form. ALL has more CNS symptoms with children include cranial nerve palsies, headache, nausea, vomiting, papilledema, and occasionally seizures and coma. Leukostasis is where the circulating blast found elevated 100000 cells/uL. It can inc blood viscosity and predisposes to leukoblastic emboli in pulmonaray and cerebral circulations. Requires immediate and effective treatment to lower blast count rapidly. Uses sphere is to remove excess blast cells, followed by chemotherapy to stop leukemic cell production in the bone marrow. Hyperuricemia occcurs as the result of inc proliferation or inc breakdown of purine nucleotides secondary to leukemic cell death that results from chemotherapy. It may inc before and during treatment. Prophylactic therapy with allopurinol, a drug that inhibits brig acid synthesis, is routinely administered to prevent renal complications secondary to Utica acid crystallization in the urine filtrate.
Diagnosis and treatment - Is based on blood and bone marrow studies; it requires the demonstration of leukemic cells in the peripheral blood, bone marrow, or extramedullary tissue. Bone marrow biopsy may be used to determine the molecular characteristics of the leukemia, the degree of bone marrow involvement, and the morphology and histology of the disease. Primary treatment is chemotherapy. It is one of the great success stories in oncology. Have led to 5 year survival rates of greater than 80% in children and 30-40% of adults Chemo lease to remission in over 50% of persons with AML, but overall survival rate is less than 30%. Bone marrow or stem cell transplantation may be considered for person with ALL and AML who have failed to respond to other forms of therapy. .
What are chronic leukemias? What are the two major types?
In contrast to acute leukemias, chronic leukemias are malignancies involving proliferation of more fully differentiated myeloid and lymphoid cells. There are two major types chronic lymphocytic leukemia CLL and chronic myeloid leukemia CML.
CLL is a global malignancy of B cells, is the most common form of leukemia in adults. Now becoming viewed as tow related entities based on aggressiveness of the disease. Some pt survive for many years without therapy and eventually succumb to unrelated diseases, whereas others have a rapidly fatal disease despite aggressive therapy. The signs are largely related to the progressive infiltration of the sbone marrow and lymphoid tissues by neoplasticism lymphocytes and to secondary immunologic defects. Are often asymptomatic at times of diagnosis, and the inc in lymphocytes is noted on a blood count for another reason. As it progresses, lymph nodes gradually inc in size and new nodes are involved in unusual areas. With aggressive form of CLL experience a more rapid sequence of lymphadenopathy, hepatosplenomegaly, fever, abdominal pain, weight loss, progressive anemia, and throbocytopenia, with a rapid rise in lymphocyte count. Hypogammaglobulinemia is common in advanced disease. Inc susceptibility to infection reflects an inability to produce specific antibodies. Diagnostic hallmark of CLL is isolated inc in lymphocytes. WBC greater than 20000 and may be elevated to several hundred thousand. Treatment usually depends on the presence of prognostic indicators. With low risk usually dont require treatment for many years . Intermediate risk may remain stable for may years as well, but some May develop complicataion and need treatment. High risk require combination chemotherapy at the times of diagnosis. In young pt with aggressive disease, an allogeneic ablative or nonmyeloablative stem cell transplant
Chronic myelogenous leukemia - is a disorder of the pluripotent hematopoietic progenitor cell. Characterized by excessive proliferation of marrow granulocytes, erythrocytes precursors, and megakaryocytes. The clinical course is commonly divided into three phases 1. A chronic phase of variable length, 2. A short accelerated phase,3. A terminal blast crisis. The onset is usually slow, with signs of weakness and weight loss, The lab finding is leukoytosis with immature granulocyte cell types in the peripheral blood. And anemia and thrombocytopenia develop. Splenomegaly is offer present at the time of diagnosis; hepatomegaly is less common and lymphadenopathy . Generally asymptomatic but without treatment most will enter the accelerated phase within 4 years. This is characterized by enlargement of the spleen and progressive symptoms splenomegaly often causes a feeling of abdominal fullness and discomfort. An inc in basophils count and more immature cells in the blood or bone marrow confirm transformation to the accelerated phase. The terminal blast crisis represents evolution to acute leukemia and is characterized by an inc number of myeloid precursors, especially blast cells in the blood. With very high blast counts > 100000 symptoms of leukostasis may occur. Prognosis is poor for this stage a median survival of 3 months.
What is malignant lymphomas? What is non-Hodgkin lymphomas?
The lymphomas are a diverse group of solid tumours composed of neoplasticism lymphoid cells that vary with respect to molecular features, genetics, clinical presentation and treatment.
The NHL are one of the most common cancers accounting for 4% of all cancers. Risk factors may affect incidence level include gender, ethnicity, chemical or radiation exposure, and immune dysfunction. 95% are adults and more than half at over 65. Cause is largely unknown. Impairment of the immune system and infectious agents may play a role. Can originate from malignant transformation of either the T or B cells during their differentiation in the peripheral lymphoid tissues. They can be in at lymphoid tissue they usually are in the lymph nodes. But all can spread to various lymphoid tissues throughout the body, especially the liver, spleen and bone marrow. A commonly used classification is the world health organization system in terms of cell type, level of maturation and a atomic sites
What’s is mature B cell lymphomas?
They are the most common type of lymphoma. Most common are the follicular lymphomas 22% and diffuse large Bcell lymphomas 31%. Small lymphocytic lymphoma, mantle cell lymphoma, peripheral T cell lymphoma and MALT lymphoma.
Follicular are derived from germinal center B cells and consist of a mixture of centroblasts and centrocytes. It predominantly affects lymph nodes but also effects spleen, bone marrow, peripheral blood, head and neck region, GI tract and skin. Most pt have advanced disease at presentation and an indolent clinical course, with a median survival of 6-10 years. 1 in 3 transforms into a fast growing diffuse large B cell lymphoma.
Diffuse large B cell lymphomas are a heterogeneous group of aggressive germinal or post germinal center neoplasms. Occurs in all ages but most in 60-70. Cause unknown, but it is rapidly evolving, multi focal, nodal and extra oral tumor. Are rapidly fatal if untreated. With intensive combination chemo, complete remission can be achieved in 60-80% of persons
Burkett lymphoma one of the most rapidly growing tumours, is also a disorder of germinal center B cells. Is the most common childhood cancer age 3-7, often begins in the jaw. Occurs where both EBV and malarial infections are common. With aggressive chemo cure rate up to 90%.
Mantle cell lymphomas less the 10% and have their origin in the naive B cell. Not in children but affect older pt. Rapid rate of progression, only 1 in 5 survives at least 5 years.
Marginal zone lymphomas involve late stage memory B cells that reside in the marginal zone or outermost compartment of the lymph node follicle. Include splenic marginal zone and MALT lymphomas of the stomach and other mucosal surfaces. Tend to remain localized for prolonged periods and to follow indolent course. Are curable by radiation or surgery when localized.
Clinical manifestation - depend of lymphoma type and stage of disease. Pt with slow growing usually present with painless lymphadenopathy, are usually disseminated at the time of diagnosis, and bone marrow involvement is frequent. Pt with intermediate usually present with accompanying constitutional symptoms such as fever, drenching night sweats, or weight loss. Inc susceptibility to bacterial, viral and fungal infections.
Diagnosis and treatment - a lymph node biopsy is used to confirm the diagnosis and immunophenotyping to determine the lineage and clonality. They can be grouped according to surface markers or phenotypic markers. Bone mararow biopsy blood studies, chest and abdominal ct scans, MRI, PET gallium scans, and bone scans may be used to stage disease. Treatment - depends on stage and clinical status of the pt. Early stage and single or limited node involvement localized radiation may be used. Most pt with indolent lymphomas have disseminated disease at the time diagnosis, so chemo and combined adjuvant radiation therapy. Pt with lymphomas that carry a risk of CNS involvement usually receive CNS prophylaxis with high doses of chemo agents and cranial irradiation. Can get to complete remission in 60-80%
What is Hodgkin lymphoma?
Is a specialized form of lymphoma that’s features the presence of an abnormal cell called a Reed-Sternberg cell. Improved treatment methods, death rates have dec 60%. Distribution of the disease is bimodal; it occurs in two separate groups 15-40 and 55 and older. Differs from NHL in many aspects. HL usually arises in a single node. Or chain of nodes and spreads first to anatomically contiguous lymphoid tissues, The staging of HL is more important. It is characterized by the presence of large, atypical, mononuclear tumor cells. These cells release factors that induce the accumulation of reactive lymphocytes, macrophages, and granulocytes,
Classification - WHO classes HL into tow major categories: Nodular lymphocyte predominant HL and classic HL. It often localized rather than disseminated at times of diagnosis, exhibits a slowly progressive course,and has a overall survival rate >80%.
Clinical Manifestations - Most pt present with painless enlargement of a single node or group of nodes. Initial lymph node is typically above the level of the diaphragm. May be complaints of chest discomfort with cough or dyspnea. Includes fever, chills, night sweats, and weight loss. Fatigue and anemioa are indicative of disease spread. In advance stages the liver, spleen lungs and digestive tract and occasionally CNS may be involved. As it progresses, the rapid proliferation of abnormal lymphocytes leads to an immunologic defect, particularly in cell mediated responses, more susceptible to infections.
Diagnosis and treatment - HL requires that the Reed-Sternberg cell be present in a biopsy specimen of lymph node tissue. CT scan of the chest and abdomen to assess involvement of mediastinal, abdominal and pelvic lymph nodes. They are staged According to the number of lymph nodes involved, whether the lymph nodes are on one or both sides of the diaphragm, and whether there is disseminated disease involving the bone marrow, liver lung or skin. It’s important because the choice of treatment and the prognosis ultimately are related to the distribution of the disease.
Treatment - irradiation and chemo are used in treating the disease.
What are plasma cell dyscrasias?
Are characterized by expansion of a single clone of immunoglobulin producing plasma cells and a resultant inc in serum levels of a single monoclonal immunoglobulin or its fragments. They include multiple myeloma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance. MGUs is characterized by the presence of the monoclonal immunoglobulin in the serum without other findings of multiple myeloma. MGU of undetermined significance is considered a premalignant condition. 2% will go on to develop a plasma cell dyscrasia.
What are multiple myeloma?
Is a B cell malignancy of terminally differentiated plasma cells. 1% of all cancers. Is higher in African American descent. And more frequently in the elderly peaking at the age of 63-70 years.
Pathogenesis - it is characterized by proliferation of malignant plasma cells in the bone marrow and osteolytic bone lesions throughout the skeletal system. It is now recognized the multiple myeloma is associated with chromosomal abnormalities, Characteristic features resulting from the proliferating neoplasticism plasma cells in multiple myeloma is the unregulated production of an abnormal monoclonal paraprotein the M protein
Manifestations - The main sites involved in multiple myeloma are the bones and bone marrow. In addition to the abnormal proliferation of marrow plasma Elle, there is proliferation and activation of osteoclasts, which leads to bone resorption and destruction. Predisposes the pt to pathologic fractures and hypercalcemia. Very high cancer ration of paraproteins may cause a hyperviscosity of body fluids. Can cause heart failure and nephropathy. Renal involvement myeloma nephrons is is a distinctive feature. Characterized by excessive production of monoclonal immunoglobulin, levels of normal immunoglobulins are usually depressed. This contributes to a general susceptibility to recurrent bacterial infections. The malignant plasma cells also can form plasma Thomas in bone and soft tissue sites. Osteolytic lesions and compression fractures may be seen in the axial skeleton and proximal long bones. Bone pain is one of the first symptoms to occur in 3/4 of all individuals. Bone destruction also impairs production of erythrocytes, leukocytes and thrombocytes.
Diagnosis and treatment - is based on clinical manifestations, blood tests, and bone marrow examination. The classic triad of bone marrow plasmacytosis, lyric bone lesions and either the serum M protein spike or the presence of Bence Jones proteins in the bring . Bone radiographs are important to establishing the presence of bone lesions. Anemia is universal. Can include hypercalcemia, an elevated erythrocyte sedimentation rate, an signs of kidney failure. Are low serum and CRP levels. Treatment is rapidly changing. Thalidomide or lenalidomide combined with dexamethasone have emerges as active agents for use in initial treatment. High dose chemo with autologous stem cell transplantataion
