Altered Leukocyte Function

Altered Hematologic Function part 2 1 Alterations in Leukocytes and Blood Coagulation 2 Leukocytes • White blood cells • Defend body through: – the inflammatory process – phagocytosis – removal of cell debris – immune reactions 3 White Blood Cell Types: Granulocytes and Agranulocytes • Granulocytes –visible granules in the cytoplasm. • Granules contain: – Enzymes – Other biochemicals that serve as signals and mediators of the inflammatory response 4 Granulocyte cell types: • Neutrophils – phagocytes • Eosinophils – red granules, associated with allergic response and parasitic worms • Basophils – deep blue granules - Release heparin, histamine and serotonin 5 6 7 8 Agranulocytes • Granules too small to be visible • Monocytes – become macrophages • Lymphocytes – B cells and T cells = immune functions 9 10 11 • WBC’s originate in red bone marrow from stem cells. • Granulocytes mature in the marrow and have a lifespan of hours to days • Agranulocytes finish maturing in blood, or in other locations. Monocytes live about 2 3 months, lymphocytes for years. 12 • Types of stem cells: – Pluripotent – Multipotent – Committed progenitor cells • Multipotent blood cells: – Common lymphoid – Common myeloid • Committed stem cell makes specific blood cells (CFU) – stimulated by erythropoietin, thrombopoietin, granulocyte-mononcyte CSF 13 • Production of WBC’s increases in response to : – Infection – Presence of steroids – Decreased reserve of leukocyte pool in bone marrow 14 WBC Abnormalities • Leukocytosis – increased numbers of WBC’s – May be a normal protective response to physiological stressors – Or may signify a disease state – a malignancy or hematologic disorder • Leukopenia – decreased numbers of WBC’s – this is never normal – Increases the risk of infections. – Agranulocytosis = granulocytopenia 15 Leukeopenia may be due to: • • • • • • • Radiation Anaphylactic shock Autoimmune disease Chemotherapeutic agents Idiosyncratic drug reactions Splenomegaly infections 16 Mononucleosis • Self-limiting lymphoproliferative disorder caused by the Epstein-Barr Virus • Infects 90% of people • Incorporates into DNA of B cells causing production of heterophil antibodies • Tc Cells are produced to limit numbers of infected B cells, accounts for increased numbers of lymphocytes. 17 Leukemia • A malignant disorder in which the bloodforming organs lose control over cell division, causing an accumulation of dysfunctional blood cells. • Uncontrolled proliferation of non-functional leukocytes crowds out normal cells from the bone marrow and decreases production of normal cells. 18 19 • Cause appears to be a genetic predisposition plus exposure to risk factors such as: – Some disorders of the bone marrow and other organs that can progress to acute leukemias – Some viruses – Ionizing radiation in large doses – Drugs – Down syndrome and other congenital disorders 20 Classification • Aleukemic leukemia • Leukemias are classified as: – acute or chronic – Myeloid or lymphoid 21 22 Acute Leukemias • Characteristics: – Abrupt onset – Rapid progression – Severe symptoms – Histological examination shows increased numbers of immature blood cells • Survival rate– Overall for acute leukemias the 5 year survival rate is about 38 %, but certain types have increased survival rates due to advances in chemotherapy. 23 24 25 Clinical manifestations • Signs and symptoms : – Fatigue – Bleeding – Fever – Anorexia and weight loss – Liver and spleen enlargement Abdominal pain and tenderness – also breast tenderness 26 • Neurologic effects are common: – Headache – Vomiting – Papilledema – swelling of the optic nerve head – a sign of increased intracranial pressure – Facial palsy – Visual and auditory disturbances – Meningeal irritation 27 • Early detection is difficult because it is often confused with other conditions. • Diagnosis is made through blood tests and examination of the bone marrow. 28 Treatment • Chemotherapy • Blood transfusions and antimicrobial, antifungal and antiviral medications • Bone marrow transplants 29 Chronic Leukemias • Characteristics: – Predominant cell is mature but doesn’t function normally – Gradual onset – Relatively longer survival time 30 • The two main types of chronic leukemia are myeloblastic and lymphocytic. • Chronic leukemia accounts for the majority of cases in adults. • Incidence increases significantly after 40 years of age. 31 Course of disease • Chronic phase of variable length (4years) • Short accelerated phase (6-12 months) • Terminal blast crisis phase (3 months) 32 • Progress slowly and insidiously. • Initial symptoms are splenomegaly, extreme fatigue, weight loss, night sweats and low grade fever. • Chronic lymphocytic leukemia involves predominantly B cells; only rarely are T lymphocytes involved. – Programmed cell death of these cells does not take place as it would normally. – These old cells do not produce antibodies effectively – Other blood cell types decrease – Infiltration of liver, spleen, lymph nodes and salivary glands. 33 Treatment • • • • Chemotherapy Monoclonal antibodies Bone marrow transplant Non-myeloablative transplant – “graft-vs.leukemia” effect. 34 Multiple Myeloma • • • • Cancer of plasma cells Osteolytic bone lesions Light chains can be toxic to kidneys Replacement of bone marrow and stimulation of osteoclasts • fractures, hypercalcemia, plasmacytomas, heart failure and neuropathy • Chemotherapy, bone marrow transplant 35 Lymphomas • These affect the secondary lymph tissue – lymph nodes, spleen, tonsils, intestinal lymphatic tissue. These may be thought of more as a solid tumor, since it occurs in solid tissue as opposed to the blood. • Two types: – Hodgkin’s Lymphoma (Disease) and – Non-Hodgkin’s Lymphoma 36 Hodgkin’s Lymphoma • Distinguished from other lymphomas by the presence of Reed-Sternberg (RS) • Begins in a single node and spreads – cancerous transformation of lymphocytes and their precursors. • Cause is believed to be genetic susceptibility and infection with the Epstein-Barr virus. • Other – tonsillectomy or appendectomy, wood working 37 http://pleiad.umdnj.edu/hemepath/T-cell/graphics/6811lennertsrscellhi.jpg 38 Clinical Manifestations • Painless swelling or lump in the neck • Asymptomatic mass in the mediastinum found on x-ray • Intermittent fever, night sweats • Weakness, weight loss • Obstruction / pressure caused by swelling lymph nodes can lead to secondary involvement of other organs. • Anemia, elevated sedimenation rate, leukocytosis, and eosinophilia 39 Treatment • Treatment: – Chemotherapy – Radiation – Prognosis good with early treatment, but early detection is difficult – The five year survival rate is 83%. 40 Non-Hodgkin’s Lymphoma • This is a generic term for a wide spectrum of disorders that cause a malignancy of the lymphoid system • Causes may be viral infections, immunosuppression, radiation, chemicals, and Helicobacter pylori. 41 • The lymphoma arises from a single cell that has alterations in its DNA. • Clinical manifestations: – Localized or generalized lymphadenopathy – Nasopharynx, GI tract, bone, thyroid, testes may be involved. 42 • With only involvement of the lymph nodes survival rate is good • Individuals with diffuse disease do not live as long. • Treatment bone marrow transplant – or autologous (from the same individual) stem cell transplant 43 Thrombocytes - platelets • Characteristics – produced by the fragmentation of megakaryocytes – so are cell fragments • Life span is about 3 days • Many are held in the spleen 44 Coagulation or Hemostasis • Soluble proteins (fibrinogen) are converted into insoluble protein threads • Many proteins and factors are part of the clotting cascade, including calcium. 45 46 47 Terminology in bleeding disorders • • • • Petechiae- pinpoint hemorrhage Purpura – larger, less regular Ecchymoses – over 2 cm – bruise Hematoma – blood trapped in soft tissue 48 Disorders of platelets • Thrombocytopenia – decreased numbers of platelets (below 100,000/mm3) • Can lead to spontaneous bleeding, if low enough, and can be fatal if bleeding occurs in the G.I. Tract, respiratory system or central nervous system. 49 • Can be congenital or acquired; acquired is more common. • Seen with: – Generalized bone marrow suppression – Acute viral infection – Nutritional deficiencies of B12, folic acid and iron – Bone marrow transplant – drugs, especially heparin, and toxins, thiazide diuretics, gold, ethanol… – Immune reactions 50 • Heparin induced thrombocytopenia is an immune mediated reaction (IgG) that causes platelet aggregation and decreased platelet counts 5 – 10 days after heparin administration in 5 – 15 % of individuals. Can cause thrombosis and emboli. 51 Thrombocythemia • This is an increased number of platelets. • If the platelet count rises high enough ( over 1 million/mm3), can get intravascular clot formation or hemorrhage. • Can be primary thrombocytothemia – cause unknown, or • Secondary thrombocytothemia – occurs after splenectomy when platelets that would normally be stored in the spleen remain in blood. – Also due to rheumatoid arthritis and cancers. 52 Disorders of Coagulation • Clotting factor disorders prevent clot formation. • May be genetic: – Hemophilia and Von Willebrand’s– genetic absence or malfunction of one of the clotting factors • Or acquired - usually due to deficient production of clotting factors by the liver: – Liver disease – Dietary deficiency of vitamin K 53