WHAT ARE THE COMPONENTS OF THE BLOOD, AND WHERE ARE THEY MADE? Plasma: proteins made mainly in liver Serum is the fluid that remains after blood clots.

WHAT ARE THE COMPONENTS OF THE WHAT ARE THE COMPONENTS OF THE BLOOD, AND WHERE ARE THEY MADE?BLOOD, AND WHERE ARE THEY MADE?

Plasma: proteins made mainly in liverSerum is the fluid that remains after blood clots

Red cells, neutrophils and platelets made in bone marrow

lymphocytes made in bone marrow, lymph nodes, spleen

BONE MARROWBONE MARROW

BONE MARROWBONE MARROW

1. Neutrophils, red cells and megakaryocytes all descended from common precursor cell called myeloid stem cell

2. Stem cells differentiate into primitive cells called blasts, which are precursors of each cell type

3. Blasts divide and mature under the influence of proteins called growth factors; as they mature they lose the ability to divide

4. Mature neutrophils and red cells enter the blood5. Megakaryocytes break into small fragments

(platelets), which enter blood

WHAT HAPPENS IN BONE MARROW?WHAT HAPPENS IN BONE MARROW?

What is a stem cell?What is a stem cell?• A cell that can reproduce itself indefinitely

– Other cells eventually stop dividing and die

• A cell that can differentiate into one or more types of functional mature cells– Other cells are “locked in” to a certain differentiation

pathway– For example, hematopoietic stem cells can differentiate into

red cells, neutrophils, megakaryocytes, or lymphocytes

• There are many types of stem cells– Usually they exist in small numbers compared to other cell

types

• In theory a single hematopoietic stem cell could re-constitute an entire bone marrow

BT

NK

BlastsStem cells Mature cells

U

L

M

rbc

pmn

megakaryocyte

E

N

M

L

lymphocytes

Differentiation

BT

NK

BlastsStem cells Mature cells

U

L

M

rbc

pmn

megakaryocyte

E

N

M

L

lymphocytes

Differentiation

DIFFERENTIATION OF DIFFERENTIATION OF NEUTROPHILS AND RED CELLSNEUTROPHILS AND RED CELLS

A megakaryocyte releasing plateletsA megakaryocyte releasing platelets

Blood 2005;106:9

Platelets

HEMATOPOIETIC GROWTH FACTORS HEMATOPOIETIC GROWTH FACTORS CONTROL PRODUCTION OF BLOOD CELLSCONTROL PRODUCTION OF BLOOD CELLS

• Growth factors regulate the growth, differentiation and function of cells of the hematopoietic and immune systems

• Examples– Erythropoietin: stimulates red cell production– Thrombopoietin: stimulates platelet production– G-CSF: stimulates granulocyte (neutrophil)

production, activates neutrophil function• These can be manufactured and given to patients to

boost production of specific blood cells

NORMAL BLOOD COUNTSNORMAL BLOOD COUNTSMen Women

White cells (thousands)

3.7-9.5 3.9-11.1

Red cells (millions)

4.3-5.7 3.9-5.0

Hemoglobin (grams/dl)

13-16.7 11.8-14.8

Hematocrit (%) 39-55 36-44

Platelets (thousands)

150,000 - 350,000

White cell, red cell and platelet numbers are per microliter of blood

HEMATOCRIT TUBESHEMATOCRIT TUBES

Anemianormal polycythemia

Functions of blood• transport oxygen, nutrients & waste products• fight infection• prevent bleeding

little bags of hemoglobinlittle bags of hemoglobin

function: carry 0function: carry 022 to tissues, CO to tissues, CO22 to lungs to lungs

hematocrihematocrit: proportion of blood volume occupied t: proportion of blood volume occupied by red cellsby red cells

RED BLOOD CELLS (ERYTHROCYTES)RED BLOOD CELLS (ERYTHROCYTES)

top side

Red blood cellsRed blood cells

RBC in small blood vessel

Red cells must be very flexibleRed cells must be very flexible

WHITE BLOOD CELLS (LEUKOCYTES)WHITE BLOOD CELLS (LEUKOCYTES)

Neutrophils• eat bacteria• produce inflammatory molecules

Lymphocytes• make antibodies• kill foreign or infected cells• regulate immune system

Monocytes• eat bacteria and other unwanted things• regulate immune system

PLATELETSPLATELETS

Smallest formed elements in blood

Not really cells (no nuclei) but fragments of large cells called megakaryocytes found mainly in bone marrow

Function: help blood clot, prevent bleeding

B lymphocytes and plasma cells T lymphocytes Natural killer (NK) lymphocytes Monocytes and macrophages

CELLS OF THE IMMUNE SYSTEMCELLS OF THE IMMUNE SYSTEM

MONOCYTESMONOCYTES

LYMPHATIC TISSUELYMPHATIC TISSUE

LYMPH NODE SPLEEN

THE LYMPHATIC SYSTEMTHE LYMPHATIC SYSTEM

WHERE LYMPHOMAS COME FROMWHERE LYMPHOMAS COME FROMor, why good lymphocytes go bador, why good lymphocytes go bad

Lymphocytes must undergo extensive rearrangement of their DNA to create a repertoire of cells capable of responding to many different antigensOccasionally this rearrangement is not accomplished

properly and the cell gains a growth advantage over its neighbors

Lymphocytes (especially B-cells) must undergo programmed cell death (apoptosis) when they are no longer neededOccasionally this program is faulty and the cells

continue to divide indefinitely

ANEMIAANEMIA

Definition: reduced total red cell mass

Hematocrit and hemoglobin concentration usually low (exception: acute blood loss)

Causes:1. blood loss2. red cell destruction (hemolysis)3. decreased red cell production

Macrocytic: big red cells Normocytic: normal size red cells Microcytic: small red cells

Reticulocytes: newly made red cells; number in blood proportional to rate of red cell production

ANEMIAANEMIA

VARIATION IN RED CELL SHAPE VARIATION IN RED CELL SHAPE IN ANEMIAIN ANEMIA

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

BT

NK

BlastsStem cells Mature cells

U

L

M

rbc

pmn

megakaryocyte

E

N

M

L

lymphocytes

Differentiation

Stem cell damageStem cell damage

BT

NK

BlastsStem cells Mature cells

U

L

M

rbc

pmn

megakaryocyte

E

N

M

L

lymphocytes

Differentiation

Defective red cell maturationDefective red cell maturation

Decreased numbers of pluripotent stem cells• cytotoxic chemicals• ionizing radiation• virus infection• "idiopathic" - probably autoimmune

Marrow empty or hypocellular Anemia, neutropenia, thrombocytopenia Treatment:

• supportive (transfusions, antibiotics etc)• immune suppression• bone marrow/stem cell transplantation

APLASTIC ANEMIA: a stem cell disorderAPLASTIC ANEMIA: a stem cell disorder

APLASTIC ANEMIAAPLASTIC ANEMIABone marrow biopsy

Normal Aplastic

ANEMIA SECONDARY TO OTHER DISEASESANEMIA SECONDARY TO OTHER DISEASES“Anemia of chronic disease”“Anemia of chronic disease”

Inflammation: infection, rheumatoid arthritis, etc Kidney failure (kidneys make erythropoietin) Cancer Malnutrition

All associated with decreased stimulus for red cell production

Nothing intrinsically wrong with bone marrow Anemia resolves if causative disorder cured

May be treatable with synthetic erythropoietin

Most common cause of anemia worldwide Decreased red cell production Microcytic: small cells due to decreased

hemoglobin production (need iron to make hemoglobin)

Causes: chronic blood loss, pregnancy, poor diet• Premenopausal women: Menstrual blood loss,

pregnancy• All others: Gastrointestinal bleeding (eg, ulcer,

cancer)• (Young children): diet of cow's milk

Treatment: replace iron, rule out/treat bleeding

IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

Normal Iron deficient (small, pale cells)

Vitamin B-12 Deficiency• Macrocytic (big cells): B-12 needed for DNA synthesis, so

cells grow but can’t divide normally• Usually due to poor absorption of vitamin rather than poor

diet • Pernicious Anemia = stomach disorder causing lack of

factor which aids B-12 absorption (intrinsic factor)• May be associated with serious neurologic disorder• Treatment: B-12 injections

Folic Acid deficiency• Macrocytic (folic acid also needed for DNA synthesis)• Causes: poor diet, alcohol abuse, certain medications• Treatment: oral folic acid supplements

ANEMIA DUE TO VITAMIN DEFICIENCYANEMIA DUE TO VITAMIN DEFICIENCY

Normal Macrocytic

Inherited disorder of hemoglobin production Caused by defect in gene(s) for either of the protein

chains in hemoglobin• alpha• beta

Microcytic anemia• Severe = thalassemia major

Most patients depend on red cell transfusion to survive• Mild or moderate = thalassemia minor

THALASSEMIATHALASSEMIA

NormalThalassemia

minor