Download Altered Hematologic Function

Altered Hematologic Function
part 2
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Alterations in Leukocytes and
Blood Coagulation
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Leukocytes
• White blood cells
• Defend body through:
– the inflammatory process
– phagocytosis
– removal of cell debris
– immune reactions
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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
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Granulocyte cell types:
• 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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Agranulocytes
• 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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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
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Leukeopenia may be due to:
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Radiation
Anaphylactic shock
Autoimmune disease
Chemotherapeutic agents
Idiosyncratic drug reactions
Splenomegaly
infections
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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.
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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.
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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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Classification
• Aleukemic leukemia
• Leukemias are classified as:
– acute or chronic
– Myeloid or lymphoid
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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.
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Clinical manifestations
• 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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Treatment
• Chemotherapy
• Blood transfusions and antimicrobial,
antifungal and antiviral medications
• Bone marrow transplants
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Chronic Leukemias
• 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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Course of disease
• 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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Treatment
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Chemotherapy
Monoclonal antibodies
Bone marrow transplant
Non-myeloablative transplant – “graft-vs.leukemia” effect.
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Multiple Myeloma
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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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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
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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
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http://pleiad.umdnj.edu/hemepath/T-cell/graphics/6811lennertsrscellhi.jpg
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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
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Treatment
• Treatment:
– Chemotherapy
– Radiation
– Prognosis good with early treatment, but early
detection is difficult
– The five year survival rate is 83%.
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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.
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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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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
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Coagulation or Hemostasis
• 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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Terminology in bleeding disorders
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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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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.
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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 B12, 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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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.
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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
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