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