altered hematologic function part 2 l.
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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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  • 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
  • Granules too small to be visible
  • Monocytes – become macrophages
  • Lymphocytes – B cells and T cells = immune functions
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
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
  • 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.
  • 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.
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
  • 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
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
Early detection is difficult because it is often confused with other conditions.
  • Diagnosis is made through blood tests and examination of the bone marrow.
  • 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
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)
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.
  • 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
  • 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

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
  • 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.
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.
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.
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
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.
  • 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