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Altered Hematologic Function part 2. Alterations in Leukocytes and Blood Coagulation. Leukocytes. White blood cells Defend body through: the inflammatory process phagocytosis removal of cell debris immune reactions. White Blood Cell Types: Granulocytes and Agranulocytes.

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leukocytes
Leukocytes
  • White blood cells
  • Defend body through:
    • the inflammatory process
    • phagocytosis
    • removal of cell debris
    • immune reactions
white blood cell types granulocytes and agranulocytes
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
granulocyte cell types
Granulocyte cell types:
  • Neutrophils – phagocytes
  • Eosinophils – red granules, associated with allergic response and parasitic worms
  • Basophils – deep blue granules - Release heparin, histamine and serotonin
agranulocytes
Agranulocytes
  • Granules too small to be visible
  • Monocytes – become macrophages
  • Lymphocytes – B cells and T cells = immune functions
slide12
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.
slide13

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
slide14
Production of WBC’s increases in response to :
    • Infection
    • Presence of steroids
    • Decreased reserve of leukocyte pool in bone marrow
wbc abnormalities
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
Leukeopenia may be due to:
  • Radiation
  • Anaphylactic shock
  • Autoimmune disease
  • Chemotherapeutic agents
  • Idiosyncratic drug reactions
  • Splenomegaly
  • infections
mononucleosis
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.
leukemia
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.
slide20
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
classification
Classification
  • Aleukemic leukemia
  • Leukemias are classified as:
    • acute or chronic
    • Myeloid or lymphoid
acute leukemias
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.
clinical manifestations
Clinical manifestations
  • Signs and symptoms :
    • Fatigue
    • Bleeding
    • Fever
    • Anorexia and weight loss
    • Liver and spleen enlargement Abdominal pain and tenderness – also breast tenderness
slide27
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
slide28
Early detection is difficult because it is often confused with other conditions.
  • Diagnosis is made through blood tests and examination of the bone marrow.
treatment
Treatment
  • Chemotherapy
  • Blood transfusions and antimicrobial, antifungal and antiviral medications
  • Bone marrow transplants
chronic leukemias
Chronic Leukemias
  • Characteristics:
    • Predominant cell is mature but doesn’t function normally
    • Gradual onset
    • Relatively longer survival time
slide31
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
Course of disease
  • Chronic phase of variable length (4years)
  • Short accelerated phase (6-12 months)
  • Terminal blast crisis phase (3 months)
slide33
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.
treatment34
Treatment
  • Chemotherapy
  • Monoclonal antibodies
  • Bone marrow transplant
  • Non-myeloablative transplant – “graft-vs.-leukemia” effect.
multiple myeloma
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
lymphomas
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
hodgkin s lymphoma
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
slide38

http://pleiad.umdnj.edu/hemepath/T-cell/graphics/6811lennertsrscellhi.jpghttp://pleiad.umdnj.edu/hemepath/T-cell/graphics/6811lennertsrscellhi.jpg

clinical manifestations39
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
treatment40
Treatment
  • Treatment:
    • Chemotherapy
    • Radiation
    • Prognosis good with early treatment, but early detection is difficult
    • The five year survival rate is 83%.
non hodgkin s lymphoma
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.
slide42
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.
slide43
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
thrombocytes platelets
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
coagulation or hemostasis
Coagulation or Hemostasis
  • Soluble proteins (fibrinogen) are converted into insoluble protein threads
  • Many proteins and factors are part of the clotting cascade, including calcium.
terminology in bleeding disorders
Terminology in bleeding disorders
  • Petechiae- pinpoint hemorrhage
  • Purpura – larger, less regular
  • Ecchymoses – over 2 cm – bruise
  • Hematoma – blood trapped in soft tissue
disorders of platelets
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.
slide50
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
slide51
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.
thrombocythemia
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.
disorders of coagulation
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