1. Decreased red cell productiona. Stem cell damage - neutrophils, platelets often
affected alsob. Defective red cell maturation
2. Increased red cell destruction (hemolysis)a. Intrinsic defect in red cell leading to
shortened lifespanb. External factors in blood or blood vessels
destroy red cells3. Blood loss
ANEMIAANEMIAClassified by cause
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 ANEMIAHEMOLYTIC ANEMIA
Hemolytic anemia: low hematocrit, plasma too yellow due to high bilirubin
INHERITED HEMOLYTIC ANEMIAINHERITED HEMOLYTIC ANEMIASickle 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
SICKLE CELL SICKLE CELL ANEMIAANEMIA
Sickle cell Normal
Sickle Cell Normal red cell
Sickle cells inflexible, can’t do this
Sickle cell anemia - pathophysiologySickle cell anemia - pathophysiology
Retinal vessel occlusion in sickle diseaseRetinal vessel occlusion in sickle disease
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
IMMUNE HEMOLYTIC ANEMIAIMMUNE HEMOLYTIC ANEMIA
TRANSFUSION REACTIONTRANSFUSION 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
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
HEMOLYTIC DISEASE OF THE NEWBORNHEMOLYTIC DISEASE OF THE NEWBORN
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
POLYCYTHEMIAPOLYCYTHEMIA
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
NEUTROPHIL DISORDERSNEUTROPHIL DISORDERS
neutrophils 0 neutrophils 19,000 neutrophils 1200
10/31/97 11/7/97 2/12/98
CANCERS OF THE BLOOD CANCERS OF THE BLOOD AND LYMPHATIC SYSTEMSAND LYMPHATIC SYSTEMS
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
LEUKEMIALEUKEMIA
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)
PATHOPHYSIOLOGY OF LEUKEMIAPATHOPHYSIOLOGY OF LEUKEMIA
Leukemia
White cells
GUM INFILTRATION IN ACUTE GUM INFILTRATION IN ACUTE LEUKEMIALEUKEMIA
SKIN INFILTRATION IN ACUTE LEUKEMIASKIN INFILTRATION IN ACUTE LEUKEMIA
CEREBRAL HEMORRHAGE CEREBRAL HEMORRHAGE IN ACUTE LEUKEMIAIN ACUTE LEUKEMIA
PURPURA IN LEUKEMIAPURPURA IN LEUKEMIA
DISSEMINATED FUNGAL INFECTION DISSEMINATED FUNGAL INFECTION IN ACUTE LEUKEMIAIN ACUTE LEUKEMIA
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%
ACUTE LEUKEMIASACUTE LEUKEMIAS
DIFFERENTIATION OF DIFFERENTIATION OF NEUTROPHILS AND RED CELLSNEUTROPHILS AND RED CELLS
Cells cannot divide
Cells capable of division
Normal AML
Bone marrow in acute leukemiaBone marrow in acute leukemia
Immature cells (blasts) in
acute myelogenous leukemia
Mature lymphocytes in chronic lymphocytic leukemia
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
CHRONIC LEUKEMIASCHRONIC LEUKEMIAS
Enlarged lymph nodes (lymphadenopathy) in chronic lymphocytic leukemia
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)
LYMPHOMASLYMPHOMAS
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
NON-HODGKIN'S LYMPHOMASNON-HODGKIN'S LYMPHOMASMany types, complex classification scheme
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
HODGKIN'S DISEASEHODGKIN'S DISEASE
“Reed-Sternberg” cell characteristic of Hodgkin’s disease
• 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 DISEASEHODGKIN’S DISEASEStaging
HODGKIN’S DISEASEHODGKIN’S DISEASEResponse to treatment
Before treatment After 6 months(Treatment completed)
After 7 years
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 MYELOMAMULTIPLE MYELOMA
MULTIPLE MYELOMAMULTIPLE MYELOMA
Plasma cellRed cells stuck together by abnormal protein (rouleaux)
BONE LESIONS IN MYELOMABONE LESIONS IN MYELOMA