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• White blood cells
• Defend body through:
– the inflammatory process
– phagocytosis
– removal of cell debris
– immune reactions
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• Granulocytes –visible granules in the cytoplasm.
• Granules contain:
– Enzymes
– Other biochemicals that serve as signals and mediators of the inflammatory response
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• Neutrophils – phagocytes
• Eosinophils – red granules, associated with allergic response and parasitic worms
• Basophils – deep blue granules - Release heparin, histamine and serotonin
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• Granules too small to be visible
• Monocytes – become macrophages
• Lymphocytes – B cells and T cells = immune functions
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• 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.
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• 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
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• Production of WBC’s increases in response to :
– Infection
– Presence of steroids
– Decreased reserve of leukocyte pool in bone marrow
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• 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
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• Radiation
• Anaphylactic shock
• Autoimmune disease
• Chemotherapeutic agents
• Idiosyncratic drug reactions
• Splenomegaly
• infections
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• 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.
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• 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.
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• 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
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• Aleukemic leukemia
• Leukemias are classified as:
– acute or chronic
– Myeloid or lymphoid
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• 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.
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• Signs and symptoms :
– Fatigue
– Bleeding
– Fever
– Anorexia and weight loss
– Liver and spleen enlargement
Abdominal pain and tenderness – also breast tenderness
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• 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
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• Early detection is difficult because it is often confused with other conditions.
• Diagnosis is made through blood tests and examination of the bone marrow.
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• Chemotherapy
• Blood transfusions and antimicrobial, antifungal and antiviral medications
• Bone marrow transplants
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• Characteristics:
– Predominant cell is mature but doesn’t function normally
– Gradual onset
– Relatively longer survival time
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• 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.
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• Chronic phase of variable length (4years)
• Short accelerated phase (6-12 months)
• Terminal blast crisis phase (3 months)
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• 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.
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• Chemotherapy
• Monoclonal antibodies
• Bone marrow transplant
• Non-myeloablative transplant – “graft-vs.leukemia” effect.
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• 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
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• 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
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• 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
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http://pleiad.umdnj.edu/hemepath/T-cell/graphics/6811lennertsrscellhi.jpg
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• 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
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• Treatment:
– Chemotherapy
– Radiation
– Prognosis good with early treatment, but early detection is difficult
– The five year survival rate is 83%.
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• 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.
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• 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.
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• 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
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• Characteristics – produced by the fragmentation of megakaryocytes – so are cell fragments
• Life span is about 3 days
• Many are held in the spleen
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• Soluble proteins (fibrinogen) are converted into insoluble protein threads
• Many proteins and factors are part of the clotting cascade, including calcium.
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• Petechiae- pinpoint hemorrhage
• Purpura – larger, less regular
• Ecchymoses – over 2 cm – bruise
• Hematoma – blood trapped in soft tissue
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• 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.
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• Can be congenital or acquired; acquired is more common.
• Seen with:
– Generalized bone marrow suppression
– Acute viral infection
– Nutritional deficiencies of B
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, folic acid and iron
– Bone marrow transplant
– drugs, especially heparin, and toxins, thiazide diuretics, gold, ethanol…
– Immune reactions
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• 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.
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• 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.
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• 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
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