Decreased red cell production

1
ANEMIA
Classified by cause

• Decreased red cell production
• Stem cell damage - neutrophils, platelets often
  affected also
• Defective red cell maturation
• Increased red cell destruction (hemolysis)
• Intrinsic defect in red cell leading to shortened
  lifespan
• External factors in blood or blood vessels
  destroy red cells
• Blood loss

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HEMOLYTIC ANEMIA

• Increased rate of red cell destruction
• Increased rate of production - increased
  reticulocytes
• Red cell destruction causes increased bilirubin
  production and jaundice
• Most red cell destruction occurs in spleen
• splenectomy may cause improvement

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Hemolytic anemia low hematocrit, plasma too
yellow due to high bilirubin
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INHERITED HEMOLYTIC ANEMIA
Sickle cell anemia

• Mutation changes structure of hemoglobin
• Mutant hemoglobin (deoxy form) polymerizes in
  cells and damages cell membranes
• membrane damage causes hemolysis
• hemoglobin crystals change cell shape to "sickle"
• sickled cells are rigid and block small blood
  vessels, causing tissue damage
• Genetics mainly affects those of African and
  Middle Eastern descent recessive inheritance
  (carriers partially protected from malaria)

O2
Sickled cell
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SICKLE CELL ANEMIA
Sickle cell
Normal
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Sickle Cell
Normal red cell
Sickle cells inflexible, cant do this
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Sickle cell anemia - pathophysiology
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Retinal vessel occlusion in sickle disease
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IMMUNE HEMOLYTIC ANEMIA

• Production of "autoantibodies" against one's own
  red cells
• Antibodies coat cells and lead to destruction in
  spleen and liver
• Positive Coombs test (detects antibodies on red
  cells) in most cases
• Treatment corticosteroids, splenectomy, i.v.
  gamma globulin

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TRANSFUSION REACTION

• Giving a person blood of the wrong type may cause
  destruction of the transfused cells (hemolysis)
  by antibodies in the recipient's blood
• The most serious reactions occur with blood
  mismatched for antigens in the ABO system
• giving O patient A, B, or AB blood
• giving A patient B or AB blood
• giving B patient A or AB blood
• In such instances there may be very rapid
  hemolysis accompanied by shock, kidney failure,
  bleeding, and death

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HEMOLYTIC DISEASE OF THE NEWBORN

• Caused by maternal antibodies against antigens on
  fetal red cells (usually Rh antigens) mother
  usually exposed (sensitized) to Rh antigen during
  prior pregnancy
• These antibodies cross the placenta and cause
  destruction of fetal red cells
• Infant liver unable to properly metabolize
  hemoglobin breakdown products (bilirubin)
• Stillbirth or anemia, jaundice, and brain damage
  may result
• Prevention prevent sensitization by giving
  antibody against Rh factor (Rhogam) to
  Rh-negative woman soon after delivery of
  Rh-positive child

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POLYCYTHEMIA

• Definition increased total red cell volume
• high hematocrit
• thick blood can cause thrombosis, other
  circulatory disorders
• Polycythemia vera increased, unregulated red
  cell production
• Most cases due to an acquired mutation in marrow
  cells that makes red cell precursors much more
  sensitive to erythropoietin
• Secondary polycythemia increased erythropoietin
  production due to decreased oxygen delivery to
  kidney
• Often due to low levels of oxygen in the blood

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NEUTROPHIL DISORDERS

• Neutropenia (decreased neutrophils)
• Decreased production (bone marrow failure, cancer
  chemotherapy)
• Increased consumption (some infections, enlarged
  spleen, autoimmune)
• Increased risk of infection when neutrophil count
  low
• Neutrophilia (increased neutrophils)
• Increased production due to physiologic stimuli
  (e.g., infection)
• Increased production due to bone marrow neoplasm

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10/31/97
11/7/97
2/12/98
neutrophils 0
neutrophils 19,000
neutrophils 1200
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CANCERS OF THE BLOOD AND LYMPHATIC SYSTEMS
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LEUKEMIA

• Malignant proliferation of white cells and/or
  their precursors (blasts)
• Myelogenous (neutrophil precursors)
• Acute myelogenous leukemia (AML)
• Chronic myelogenous leukemia (CML)
• Lymphocytic
• Acute lymphocytic leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)
• Chronic leukemias more mature cells,
  slow-growing
• Acute leukemias immature cells (blasts),
  fast-growing

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PATHOPHYSIOLOGY OF LEUKEMIA

• Bone marrow failure (marrow fills with leukemic
  cells)
• anemia
• neutropenia (infections)
• thrombocytopenia (bleeding)
• Leukemic cells in blood may impair circulation
• Leukemic cells in other organs
• spleen, lymph nodes
• skin
• brain
• Toxic substances from leukemic cells
• uric acid (gout, kidney failure)
• proteolytic enzymes (tissue damage, bleeding)

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White cells
Leukemia
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GUM INFILTRATION IN ACUTE LEUKEMIA
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SKIN INFILTRATION IN ACUTE LEUKEMIA
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CEREBRAL HEMORRHAGE IN ACUTE LEUKEMIA
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PURPURA IN LEUKEMIA
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DISSEMINATED FUNGAL INFECTION IN ACUTE LEUKEMIA
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ACUTE LEUKEMIAS

• Acute myelogenous leukemia (AML)
• adults gt children
• fatal if untreated
• remission, occasional cure possible with
  intensive chemotherapy
• sometimes curable with bone marrow transplant
• Acute lymphocytic leukemia (ALL)
• children and adults (most common childhood
  leukemia)
• fatal if untreated
• curable with chemotherapy or bone marrow
  transplantation
• Cure rates in children gt 75

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DIFFERENTIATION OF NEUTROPHILS AND RED CELLS
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Bone marrow in acute leukemia
Normal
AML
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Immature cells (blasts) in acute myelogenous
leukemia
Mature lymphocytes in chronic lymphocytic leukemia
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CHRONIC LEUKEMIAS

• Chronic myelogenous leukemia (CML)
• rare in children
• treatable but often fatal within 5-10 years
• Newer treatments will probably improve the
  prognosis
• may be curable with bone marrow transplantation
• Chronic lymphocytic leukemia (CLL)
• almost all patients middle-aged and older
• treatable but incurable
• not all patients need treatment, many live gt 10
  years

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Enlarged lymph nodes (lymphadenopathy) in chronic
lymphocytic leukemia
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LYMPHOMAS

• Cancer of lymphocytes or their precursors
• Forms tumors in lymph nodes, spleen, bone marrow,
  other organs
• Sometimes in blood - overlap with lymphoid
  leukemia
• Many different kinds - spectrum of severity
• Hodgkin's vs non-Hodgkin's
• B-cell vs T-cell
• Mature vs immature lymphoid cells
• Fast vs slow-growing
• Usually treatable, sometimes curable
  (chemotherapy, radiation, marrow transplantation)

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NON-HODGKIN'S LYMPHOMAS
Many types, complex classification scheme

• LOW GRADE
• Cells appear mature
• Good news slow-growing - patients may live many
  years with disease
• Bad news treatable but generally incurable
• Usually affect older people
• HIGH GRADE
• Cells less mature
• The most aggressive forms resemble acute
  lymphoblastic leukemia
• Good news often curable with chemotherapy
• Bad news faster-growing, fatal in months if not
  treated or treatment doesn't work
• Some varieties occur in children
• Example Burkitt lymphoma (resembles acute
  leukemia)
• Rule of thumb the less mature the cancer cell,
  the faster growing the lymphoma, and the more
  likely the disease is to affect younger people
  and to be curable

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HODGKIN'S DISEASE

• Probably a cancer of lymphocytes (lymphoma)
• Almost always begins in lymph nodes
• Spreads gradually to other lymph nodes organs
• stage extent of spread
• Relatively common in young adults
• Curable in many cases with radiation or
  chemotherapy

Reed-Sternberg cell characteristic of Hodgkins
disease
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HODGKINS DISEASE
Staging

• Stage I single lymph node or contiguous group
  of nodes
• Stage II more than one node group, same side of
  diaphragm
• Stage III confined to nodes (and/or spleen) but
  present on both sides of diaphragm
• Stage IV spread outside nodes (liver, bone
  marrow, lung, etc)
• Presence of symptoms (fever, weight loss, night
  sweats) designated by "B" after stage (no
  symptoms "A")
• Lower stage disease often treated with
  radiotherapy higher stage disease with
  chemotherapy

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HODGKINS DISEASE Response to treatment
Before treatment
After 6 months (Treatment completed)
After 7 years
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MULTIPLE MYELOMA

• Cancer of plasma cells (antibody-producing cells)
• Most patients have monoclonal immunoglobulin
  (antibody-like protein) in blood or urine
• This protein may damage kidneys, other organs
• Bone destruction, bone marrow failure common

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MULTIPLE MYELOMA
Red cells stuck together by abnormal protein
(rouleaux)
Plasma cell
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BONE LESIONS IN MYELOMA