what are the components of the blood, and where are they made? plasma: proteins made mainly in liver...
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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