... and platelet-derived growth factor (PDGF) Hemostasis

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Blood
Ch 19
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Blood
Artery
White blood cells
Platelets
Red blood cells
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Function Blood

• Deliver O2
• Remove metabolic wastes
• Maintain temperature, pH, and fluid volume
• Protection from blood loss- platelets
• Prevent infection- antibodies and WBC
• Transport hormones

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Blood
Plasma-55
Buffy coat-lt1
Formed elements-45
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Blood Plasma Components-55

• 90 Water
• 8 Solutes
• Proteins
• Albumin (60 )
• Alpha and Beta Globulins
• Gamma Globulins
• fibrinogens
• Gas
• Electrolytes

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Blood Plasma Components

• Organic Nutrients
• Carbohydrates
• Amino Acids
• Lipids
• Vitamins
• Hormones
• Metabolic waste
• CO2
• Urea

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Buffy Coat- lt1

• Leukocytes
• Platelets

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Formed Elements of the Blood-45

• Erythrocytes (red blood cells)
• Leukocytes (white blood cells)
• Platelets (thrombocytes)

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Erythrocytes
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Erythrocyte?7.5?m in dia    Anucleate- so can't
reproduce however, repro in red bone marrow   
Hematopoiesis- production of RBC    Function-
transport respiratory gases    Hemoglobin-
quaternary structure, 2 ? chains and 2 ?
chains    Lack mitochondria. Why?   1 RBC
contains 280 million hemoglobin
molecules    Men- 5 million cells/mm3    Women-
4.5 million cells/mm3    Life span 100-120 days
and then destroyed in spleen (RBC graveyard)
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Hemoglobin
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Hematopoiesis

• Hematopoiesis (hemopoiesis) blood cell formation
  
• Occurs in red bone marrow of axial skeleton,
  girdles and proximal epiphyses of humerus and
  femur

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Hematopoiesis

• Hemocytoblasts (hematopoietic stem cells)
• Give rise to all formed elements
• Hormones and growth factors push the cell toward
  a specific pathway of blood cell development
• New blood cells enter blood sinusoids

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Erythropoiesis

• Erythropoiesis red blood cell production
• A hemocytoblast is transformed into a
  proerythroblast
• Proerythroblasts develop into early erythroblasts

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Erythropoiesis

• Phases in development
• Ribosome synthesis
• Hemoglobin accumulation
• Ejection of the nucleus and formation of
  reticulocytes
• Reticulocytes then become mature erythrocytes

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Stem cell
Committed cell
Developmental pathway
Phase 1 Ribosome synthesis
Phase 2 Hemoglobin accumulation
Phase 3 Ejection of nucleus
Reticulo- cyte
Erythro- cyte
Proerythro- blast
Early erythroblast
Late erythroblast
Normoblast
Hemocytoblast
Figure 17.5
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Regulation of Erythropoiesis

• Too few RBCs leads to tissue hypoxia
• Too many RBCs increases blood viscosity
• Balance between RBC production and destruction
  depends on
• Hormonal controls
• Adequate supplies of iron, amino acids, and B
  vitamins

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Hormonal Control of Erythropoiesis

• Erythropoietin (EPO)
• Direct stimulus for erythropoiesis
• Released by the kidneys in response to hypoxia

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Hormonal Control of Erythropoiesis

• Causes of hypoxia
• Hemorrhage or increased RBC destruction reduces
  RBC numbers
• Insufficient hemoglobin (e.g., iron deficiency)
• Reduced availability of O2 (e.g., high altitudes)

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Hormonal Control of Erythropoiesis

• Effects of EPO
• More rapid maturation of committed bone marrow
  cells
• Increased circulating reticulocyte count in
  12 days
• Testosterone also enhances EPO production,
  resulting in higher RBC counts in males

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Formation Destruction of RBCs
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RBC Diseases
Anemia- when blood has low O2 carrying capacity
insufficient RBC or iron deficiency. Factors that
can cause anemia- exercise, B12
deficiency Polycythemia- excess of erythrocytes,
? viscosity of blood 8-11 million
cells/mm3 Usually caused by cancer, tissue
hypoxia, dehydration however, naturally occurs
at high elevations Blood doping- in
athletes?remove blood 2 days before event and
then replace it Epoetin- banned by Olympics.
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RBC Diseases
Sickle-cell anemia- HbS results from a change in
just one of the 287 amino acids in the ? chain in
the globin molecule. Found in 1 out of 400
African Americans. Abnormal hemoglobin
crystalizes when O2 content of blood is low,
causing RBCs to become sickle-shaped. Homozygous
for sickle-cell is deadly, but in malaria
infested countries, the heterozygous condition is
beneficial.
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Genetics of Sickle Cell Anemia
Genetics of Sickle Cell Anemia
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Types of Leukocytes
4,000-11,000 cells/mm 3
Never let monkeys eat bananas

• Granulocytes
• Neutrophils- 40-70
• Eosinophils- 1-4
• Basophils- lt1
• Agranulocytes
• Monocytes- 4-8
• Lymphocytes- 20-45

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Lymphocyte
Eosinophil
Basophil
platelet
Neutrophil
Monocyte
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eosinophil
neutrophil
monocyte
RBC
neutrophil
monocyte
lymphocyte
lymphocyte
basophil
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ID WBCs
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Leukocyte Squeezing Through Capillary Wall
Diapedesis
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WBC Diseases

• Leukopenia
• Abnormally low WBC countdrug induced
• Leukemias
• Cancerous conditions involving WBCs
• Named according to the abnormal WBC clone
  involved
• Mononucleosis
• highly contagious viral disease caused by
  Epstein-Barr virus excessive of agranulocytes
  fatigue, sore throat, recover in a few weeks

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Platelets

• Small fragments of megakaryocytes
• Formation is regulated by thrombopoietin
• Blue-staining outer region, purple granules
• Granules contain serotonin, Ca2, enzymes, ADP,
  and platelet-derived growth factor (PDGF)

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Stem cell
Developmental pathway
Hemocyto- blast
Promegakaryocyte
Megakaryoblast
Megakaryocyte
Platelets
Figure 17.12
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Hemostasis- stoppage of bleeding
Platelets 250,000-500,000 cells/mm3
Tissue Damage
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Hemostasis

• Vessel injury

2. Vascular spasm
3. Platelet plug formation
4. Coagulation
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Hemostasis( feedback)
Traps RBC platelets
Platelets release thromboplastin
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Blood Clot
RBC
Platelet
Fibrin thread
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Disorders of Hemostasis

• Thromboembolytic disorders undesirable clot
  formation
• Bleeding disorders abnormalities that prevent
  normal clot formation

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Thromboembolytic Conditions

• Thrombus clot that develops and persists in an
  unbroken blood vessel
• May block circulation, leading to tissue death
• Embolus a thrombus freely floating in the blood
  stream
• Pulmonary emboli impair the ability of the body
  to obtain oxygen
• Cerebral emboli can cause strokes

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Thromboembolytic Conditions

• Prevented by
• Aspirin
• Antiprostaglandin that inhibits thromboxane A2
• Heparin
• Anticoagulant used clinically for pre- and
  postoperative cardiac care
• Warfarin
• Used for those prone to atrial fibrillation

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Bleeding Disorders

• Thrombocytosis- too many platelets due to
  inflammation, infection or cancer
• Thrombocytopenia- too few platelets
• causes spontaneous bleeding
• due to suppression or destruction of bone marrow
  (e.g., malignancy, radiation)
• Platelet count lt50,000/mm3 is diagnostic
• Treated with transfusion of concentrated
  platelets
•  

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Bleeding Disorders

• Impaired liver function
• Inability to synthesize procoagulants
• Causes include vitamin K deficiency, hepatitis,
  and cirrhosis
• Liver disease can also prevent the liver from
  producing bile, impairing fat and vitamin K
  absorption

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Bleeding Disorders

• Hemophilias include several similar hereditary
  bleeding disorders
• Symptoms include prolonged bleeding, especially
  into joint cavities
• Treated with plasma transfusions and injection of
  missing factors

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Hemophiliac- a sex-linked recessive trait,
primarily carried by males (x chromosome)
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Blood Types
Type A Type B Type AB Type O
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Blood Typing
Blood type is based on the presence of 2 major
antigens in RBC membranes-- A and B Blood
type Antigen Antibody A A
anti-B B B anti-A A B
AB no anti body Neither A or B
O anti-A and anti-B Antigen- protein on the
surface of a RBC membrane Antibody-
proteins made by lymphocytes in plasma which are
made in response to the presence of
antigens. They attack foreign antigens, which
result in clumping (agglutination)
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Type A
ABO Blood Types
b
b
Produces anti-B antibodies
b
b
b
b
b
b
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Type B
ABO Blood Types
a
a
a
Produces anti-A antibodies
a
a
a
a
a
a
a
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Type AB
ABO Blood Types
Produces neither anti-A nor anti-B antibodies
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Type O
ABO Blood Types
b
a
b
a
a
Produces both anti-A and anti-B antibodies
b
a
b
a
a
b
a
b
a
a
a
b
b
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Rh Factor and Pregnancy
RH indicates protein
RH indicates protein
RH- indicates no protein
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Rh Factor and Pregnancy
Rh mother w/Rh- baby no problem Rh- mother
w/Rh baby problem Rh- mother w/Rh- father no
problem Rh- mother w/Rh- baby-- no problem
RhoGAM used _at_ 28 weeks
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Type AB- universal recipients Type O- universal
donor   Rh factor Rh 85 dominant in pop Rh-
15 recessive Blood Type Clumping Antibody A
antigen A anti-A serum antibody
anti-b B antigen B anti-B serum antibody
anti-a AB antigen A B anti A B serum
- O neither A or B no clumping w/ either anti A
or B anti-a, anti-b
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Serum
Blood being tested
Anti-A
Anti-B
Type AB (contains agglutinogens A and
B agglutinates with both sera)
RBCs
Type A (contains agglutinogen A agglutinates
with anti-A)
Type B (contains agglutinogen B agglutinates
with anti-B)
Type O (contains no agglutinogens does
not agglutinate with either serum)
Figure 17.16
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ABO Blood Types
Phenotype Genotype O i i A I A I A or I A
i B I B I B or I B i AB I A I B
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Punnett square
Type A and Type B cross
i
IB
IAi
IAIB
IA
IA
IAi
IAIB
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INQUIRY

• What is an erythrocyte, leukocyte, and
  thrombocyte?
• What 2 things do red cells lack compared to white
  cells?
• What dietary component is needed for the
  production of red blood cells?
• The largest cells in the blood that leave the
  bloodstream to become macrophages are ____.
• In an acute infection, the white cell count would
  show as ______.
• Erythroblastosis fetalis , also known as
  hemolytic newborn disease, occurs in ____ mothers
  carrying ____ fetuses.
• What antigens and antibodies found on AB red
  cells?
• In a transfusion, what type blood can you give a
  type O person?