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Module 2: Symptoms and syndromes in diseases of internal organs.doc
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Additional methods of examination

Clinical blood analysis: leucocytosis 30-300xl09/l; the white blood cells count may be normal or even decreased; red blood cells count decreased; hemoglobin concentration decreased; severe thrombocytopenia; blast cells - 95%.

Blood film examination show variable numbers of blast cells. In patients with acute myeloblastic leukemia the blast cells are the myeloblasts or erythroblasts. The blasts may show Auer rods and other abnormal cells may be present: promyelocytes, myelocytes, agranular neutrophils;

absence of eoisinophyls and basophils.

Bone morrow: bone marrow is hypercellular with a marked proliferation of blast cells which typically amount to over 75 % of the marrow cell total.

Chronic myelocytic leukemia

Chronic myelocytic leukemia - is defined as the myeloproliferative disorders. Chronic myelocytic leukemia is as a neoplastic disease of bone marrow stem cell -precursor of myelopoiesis, which is common for granulocytes, erythrocytes and megakariocytes with excessive production of granulocytes in the bone marrow and other hematopoietic organs.

Etiology

The specific factors haven't been established. The causative agents of chronic myelocytic leukemia arc suspected such as ionizing radiation, exposure some chemical carcinogens, which damage bone marrow.

Pathogenesis

Excess radiation or mutagenic chemicals cause mutation in the bone marrow stem cell, damage of DNA, and transformation it in neoplastic cell with chromosomal disorders. This cell produces clones of changed bone marrow stem cells with abnormal chromosome, known as Philadelphia chromosome, resulting from the translocation of chromosome 22 to chromosome 9. This chromosomal abnormality leads to the formation new onkogene bcr/abl which processes an increased enzyme activity. Clones of bone marrow stem cells develop an ability to proliferate excessively, especially the granulocytic cell lines, resulting in a tremendous increase in leukocytes in the peripheral blood stream. Some of these cells preserve the ability to differentiate in mature cells. Bone marrow may be further damaged by infiltration abnormal cells with replacement of normal hematopoietic process because interfere with normal production of hemapoietic cell lines. Continuous proliferation of mutative cells promotes their expansion in the organs and tissue in a form of metastasizing tumor cells.

Clinical features

The presence of neoplastic bone marrow element shows the following consequences. Increased nonfunctional white blood cell production and decreased normal white blood cell production result in infections. Decreased red blood cell production leads to anemia. Decreased platelet production will result in a greater tendency to bleeding. There are three clinical stages of disease: stage I - initial, stage II - accelerated phase, stage III - dystrophy and blast crisis. The disease develops gradually. The initial symptoms and signs are not specific such as general malaise, fatigue, weight loss, low-grade fever. These disorders are detected accidentally as a rule. Some patients are symptomatic at diagnosis. In the pronounced stage weakness becomes considerable, night sweating profuse, elevation of temperature periodically to 37,5-39°C, pain in the left hypochondrium, abdominal fullness and discomfort. Myeloid infiltration in the lung can be caused some additional symptoms, such as coughing. Many patients will complain on pain of the bones especially the sternum and ribs, which are the major sites of blood cell production.

Objeсtivel examination reveals pallid skin with yellowish or grayish tint due to the anemia. The specific sign of disease is skin leukemic infiltration and local lesions. Infiltrations of the bones and the joints may cause localized lesions. Features of anemia may include dyspnea and tachycardia, lethargy. Chronic myelocytic leukemia is associated with increased susceptibility to infections such as pneumonia, pleuritis, pyelonephritis.

In patients occurs considerable nonsymmetrical enlargement of abdomen predominantly in the left hypochondrium, due to the marked enlarged spleen. In about 10 % patients the enlargement is massive, extending to over 15 cm below the costal margin. The spleen is usually firm, smooth and painless. The presence of splenomegaly may be explained by excessive work to eliminate senescent and abnormal white blood cells. Enlarged liver is fairly common also. Less common neurological presentations include dizziness, visual disturbances, convulsions, paralysis resulting from the affection of the brain and spinal cord.

In patients is common bleeding syndrome with bruising, epitasis, menorrhagia or hemorrhage from other sites.

In stage III may observe cachexia, secondary prolonged infections, progressive anemia, great tendency to bleeding. Finally, this chronic condition may transform to blast crises similar to an acute form of leukemia with the production of large number of immature myeloblasts in the bone marrow and the bloodstream. This new blastic phase is fatal.

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