Transcript Increased red cell destruction (hemolysis)

ANEMIA
Classified by cause
1.
Decreased red cell production
a. Stem cell damage - neutrophils, platelets often
affected also
b. Defective red cell maturation
2.
Increased red cell destruction (hemolysis)
a. Intrinsic defect in red cell leading to
shortened lifespan
b. External factors in blood or blood vessels
destroy red cells
3.
Blood loss
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
Hemolytic anemia: low hematocrit, plasma too yellow due to high bilirubin
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
O
2
“Sickled” cell
 Genetics: mainly affects those of African and Middle
Eastern descent; recessive inheritance (carriers
partially protected from malaria)
SICKLE CELL ANEMIA
Sickle cell
Normal
Sickle Cell
Normal red cell
Sickle cells inflexible,
can’t do this
Sickle cell anemia - pathophysiology
Retinal vessel occlusion in sickle disease
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
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
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
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
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
10/31/97
neutrophils 0
11/7/97
neutrophils 19,000
2/12/98
neutrophils 1200
CANCERS OF THE BLOOD
AND LYMPHATIC SYSTEMS
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), fastgrowing
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)
White cells
Leukemia
GUM INFILTRATION IN ACUTE LEUKEMIA
SKIN INFILTRATION IN ACUTE LEUKEMIA
CEREBRAL HEMORRHAGE
IN ACUTE LEUKEMIA
PURPURA IN LEUKEMIA
DISSEMINATED FUNGAL INFECTION
IN ACUTE LEUKEMIA
ACUTE LEUKEMIAS
 Acute myelogenous leukemia (AML)
• adults > 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 > 75%
DIFFERENTIATION OF
NEUTROPHILS AND RED CELLS
Cells capable of division
Cells cannot divide
Bone marrow in acute leukemia
Normal
AML
Immature cells (blasts) in
acute myelogenous
leukemia
Mature lymphocytes in
chronic lymphocytic leukemia
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 > 10
years
Enlarged lymph
nodes
(lymphadenopathy)
in chronic
lymphocytic
leukemia
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)
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
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
Hodgkin’s disease
HODGKIN’S 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
HODGKIN’S DISEASE
Response to treatment
Before treatment
After 6 months
(Treatment
completed)
After 7 years
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
MULTIPLE MYELOMA
Red cells
stuck
together by
abnormal
protein
(rouleaux)
Plasma cell
BONE LESIONS IN MYELOMA