2 Alterations in Leukocytes and Blood Coagulation
3 Leukocytes White blood cells Defend body through: – the inflammatory process – phagocytosis –removal of cell debris – immune reactions
4 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
5 Granulocyte cell types: Neutrophils – phagocytes Eosinophils – red granules, associated with allergic response and parasitic worms Basophils – deep blue granules - Release heparin, histamine and serotonin
12 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.
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
14 Production of WBC’s increases in response to : –Infection –Presence of steroids –Decreased reserve of leukocyte pool in bone marrow
15 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
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
18 Leukemia A malignant disorder in which the blood- forming 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.
20 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
21 Classification Aleukemic leukemia Leukemias are classified as: – acute or chronic –Myeloid or lymphoid
23 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.
26 Clinical manifestations Signs and symptoms : –Fatigue –Bleeding –Fever –Anorexia and weight loss –Liver and spleen enlargement Abdominal pain and tenderness – also breast tenderness
27 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
28 Early detection is difficult because it is often confused with other conditions. Diagnosis is made through blood tests and examination of the bone marrow.
29 Treatment Chemotherapy Blood transfusions and antimicrobial, antifungal and antiviral medications Bone marrow transplants
30 Chronic Leukemias Characteristics: –Predominant cell is mature but doesn’t function normally –Gradual onset –Relatively longer survival time
31 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.
Course of disease Chronic phase of variable length (4years) Short accelerated phase (6-12 months) Terminal blast crisis phase (3 months) 32
33 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.
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
36 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
37 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
39 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
40 Treatment Treatment: –Chemotherapy –Radiation –Prognosis good with early treatment, but early detection is difficult –The five year survival rate is 83%.
41 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.
42 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.
43 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
44 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
45 Coagulation or Hemostasis Soluble proteins (fibrinogen) are converted into insoluble protein threads Many proteins and factors are part of the clotting cascade, including calcium.
48 Terminology in bleeding disorders Petechiae- pinpoint hemorrhage Purpura – larger, less regular Ecchymoses – over 2 cm – bruise Hematoma – blood trapped in soft tissue
49 Disorders of platelets Thrombocytopenia – decreased numbers of platelets (below 100,000/mm 3 ) 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.
50 Can be congenital or acquired; acquired is more common. Seen with: –Generalized bone marrow suppression –Acute viral infection –Nutritional deficiencies of B 12, folic acid and iron –Bone marrow transplant –drugs, especially heparin, and toxins, thiazide diuretics, gold, ethanol… –Immune reactions
51 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.
52 Thrombocythemia This is an increased number of platelets. If the platelet count rises high enough ( over 1 million/mm 3 ), 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.
53 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