Artery

White blood cells

Platelets

Red blood cells

Blood Facts
The average adult has about FIVE liters of blood inside of their body, which makes up 7-8% of their body weight.
Blood is living tissue that carries oxygen and nutrients to all parts of the body, and carries carbon dioxide and other waste products back to the lungs, kidneys and liver for disposal. It also fights against infection and helps heal wounds, so we can stay healthy. There are about one billion red blood cells in two to three drops of blood. For every 600 red blood cells, there are about 40 platelets and one white cell.
http://www.bloodbankofalaska.org/about_blood/index.html

 Deliver O2

Remove metabolic wastes

Maintain temperature, pH, and fluid volume

Protection from blood loss- platelets

Prevent infection- antibodies and WBC Transport hormones

Functions of Blood
Transport of:
Gases, nutrients, waste products Processed molecules Regulatory molecules

Regulation of pH and osmosis Maintenance of body temperature Protection against foreign substances Clot formation
19-4

Plasma-55% Buffy coat-<1%

Formed elements-45%

Plasma
Liquid part of blood
Pale yellow made up of 91% water, 9% other

Colloid: Liquid containing suspended substances that dont settle out

Albumin: Important in regulation of water movement between tissues and blood Globulins: Immune system or transport molecules Fibrinogen: Responsible for formation of blood clots
19-6

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

Organic Nutrients

Carbohydrates

Amino Acids

Lipids

Vitamins

Hormones

Metabolic waste

CO2

Urea

 Leukocytes
Platelets

 Erythrocytes (red blood cells)

Leukocytes (white blood cells)

Platelets (thrombocytes)

Formed Elements
Red blood cells (erythrocytes) White blood cells (leukocytes)
Granulocytes
Neutrophils Eosinophils Basophils

Agranulocytes
Lymphocytes Monocytes

Platelets (thrombocytes)
19-11

Production of Formed Elements

Hematopoiesis or hemopoiesis: Process of blood cell production Stem cells: All formed elements derived from single population
Proerythroblasts: Develop into red blood cells Myeloblasts: Develop into basophils, neutrophils, eosinophils Lymphoblasts: Develop into lymphocytes Monoblasts: Develop into monocytes Megakaryoblasts: Develop into platelets
19-12

Hematopoiesis

19-13

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

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

Formation & Destruction of RBCs

Erythropoiesis

Production of red blood cells

Stem cells proerythroblasts early erythroblasts intermediate late reticulocytes

Erythropoietin: Hormone to stimulate RBC production

19-18

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

Erythropoiesis
Phases in development
1. Ribosome synthesis 2. Hemoglobin accumulation 3. Ejection of the nucleus and formation of reticulocytes

Reticulocytes then become mature erythrocytes

Stem cell

Committed cell

Developmental pathway Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus

Hemocytoblast

Proerythroblast

Early erythroblast

Late erythroblast

Normoblast

Reticulocyte

Erythrocyte

Figure 17.5

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

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)

Hormonal Control of Erythropoiesis

Effects of EPO
More rapid maturation of committed bone marrow cells Increased circulating reticulocyte count in 1 2 days

Testosterone also enhances EPO production, resulting in higher RBC counts in males

Hormonal Control of Erythropoiesis

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

Hemoglobin Breakdown

19-26

Erythrocytes
Structure
Biconcave, anucleate

Components
Hemoglobin Lipids, ATP, carbonic anhydrase

Function
Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs
19-27

Hemoglobin

Consists of:
4 globin molecules: Transport carbon dioxide (carbonic anhydrase involved), nitric oxide 4 heme molecules: Transport oxygen
Iron is required for oxygen transport
19-28

Leukocytes
Protect body against Types Neutrophils: Most common; microorganisms and phagocytic cells destroy bacteria remove dead cells and (60%) debris Eosinophils: Detoxify chemicals; Movements reduce inflammation (4%)
Ameboid Diapedesis Chemotaxis Passive Immunity Active Immunity Antigen Antibody Basophils: Alergic reactions; Release histamine, heparin increase inflam. response (1%) Lymphocytes: Immunity 2 types; b & t Cell types. IgG-infection, IgMmicrobes, IgA-Resp & GI, IgEAlergy, IgD-immune response Monocytes: Become macrophages
19-29

Leukocytes

19-30

Thrombocytes
Cell fragments pinched off from megakaryocytes in red bone marrow Important in preventing blood loss
Platelet plugs Promoting formation and contraction of clots
19-31

Hemostasis
Arrest of bleeding Events preventing excessive blood loss
Vascular spasm: Vasoconstriction of damaged blood vessels Platelet plug formation Coagulation or blood clotting

19-32

Platelet Plug Formation

19-33

Coagulation
Stages
Activation of prothrombinase Conversion of prothrombin to thrombin Conversion of fibrinogen to fibrin

Pathways
Extrinsic Intrinsic
19-34

Clot Formation

19-35

Fibrinolysis

Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin

19-36

Blood Grouping
Determined by antigens (agglutinogens) on surface of RBCs Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs Groups
ABO and Rh

19-37

ABO Blood Groups

19-38

Agglutination Reaction

19-39

Rh Blood Group
First studied in rhesus monkeys Types
Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present

Hemolytic disease of the newborn (HDN)

Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs
19-40

Erythroblastosis Fetalis

19-41

Diagnostic Blood Tests

Type and crossmatch Complete blood count
Red blood count Hemoglobin measurement Hematocrit measurement

White blood count Differential white blood count Clotting

19-42

Blood Disorders
Erythrocytosis: RBC overabundance Anemia: Deficiency of hemoglobin
Iron-deficiency Pernicious Hemorrhagic Hemolytic Sickle-cell

Hemophilia Thrombocytopenia Leukemia Septicemia Malaria Infectious mononucleosis Hepatitis

19-43

Erythrocytes

Erythrocyte7.5m 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)

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

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

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

Erythropoiesis
Phases in development
1. Ribosome synthesis 2. Hemoglobin accumulation 3. Ejection of the nucleus and formation of reticulocytes

Reticulocytes then become mature erythrocytes

Stem cell

Committed cell

Developmental pathway Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus

Hemocytoblast

Proerythroblast

Early erythroblast

Late erythroblast

Normoblast

Reticulocyte

Erythrocyte

Figure 17.5

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

Hormonal Control of Erythropoiesis

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

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)

Hormonal Control of Erythropoiesis

Effects of EPO
More rapid maturation of committed bone marrow cells Increased circulating reticulocyte count in 1 2 days

Testosterone also enhances EPO production, resulting in higher RBC counts in males

Formation & Destruction of RBCs

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 athletesremove blood 2 days before event and then replace it; Epoetin;- banned by Olympics.

Sickle-cell anemiaHbS 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.

Genetics of Sickle Cell Anemia

Genetics of Sickle Cell Anemia

4,000-11,000 cells/mm 3 Never let monkeys eat bananas

Granulocytes Neutrophils- 40-70% Eosinophils- 1-4% Basophils- <1% Agranulocytes Monocytes- 4-8% Lymphocytes- 20-45%

Basophil

Eosinophil

Lymphocyte

platelet

Neutrophil

Monocyte

eosinophil neutrophil monocyte RBC neutrophil monocyte

lymphocyte

basophil

lymphocyte

ID WBCs

Leukocyte Squeezing Through Capillary Wall

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

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)

Stem cell

Developmental pathway

Hemocytoblast

Promegakaryocyte Megakaryoblast Megakaryocyte Platelets

Figure 17.12

Hemostasis- stoppage of bleeding

Platelets: 250,000-500,000 cells/mm3

Tissue Damage

Platelet Plug Clotting Factors

Hemostasis:
1. Vessel injury

2. Vascular spasm
3. Platelet plug formation

4. Coagulation

Hemostasis
(+ feedback)

Clotting Factors
thromboplastin

Prothrombin

Thrombin

Fibrinogen

Fibrin
Traps RBC & platelets
Platelets release thromboplastin

Blood Clot
RBC

Platelet

Fibrin thread

Disorders of Hemostasis
Thromboembolytic disorders: undesirable clot formation Bleeding disorders: abnormalities that prevent normal clot formation

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

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

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 <50,000/mm3 is diagnostic Treated with transfusion of concentrated platelets

 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

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

Hemophiliac- a sex-linked recessive trait, primarily carried by males (x chromosome)

Type A Type B Type AB Type O

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)

ABO Blood Types

b b

b b

Type A

Produces anti-B antibodies

b

ABO Blood Types

a a a a a

Type B

Produces anti-A antibodies

a a

ABO Blood Types

Type AB

Produces neither anti-A nor anti-B antibodies

ABO Blood Types

b b a a b a a b a a b a b a

a b

Type O

Produces both anti-A and anti-B antibodies

b a

Rh Factor and Pregnancy

RH+ indicates protein RH- indicates no protein

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 @ 28 weeks

Type AB- universal recipients Type O- universal donor

Rh factor: Rh+ 85% dominant in pop Rh- 15% recessive

Blood Type A B AB antigen A antigen B antigen A & B

Clumping anti-A serum anti-B serum anti A & B serum

Antibody antibody anti-b antibody anti-a -

neither A or B

no clumping w/ either anti A or B

anti-a, anti-b

Blood being tested Type AB (contains agglutinogens A and B; agglutinates with both sera) 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)

Anti-A

Serum

Anti-B

RBCs

Figure 17.16

Blood Type & Rh

How Many Have It

Frequency

O O

Rh Positive Rh Negative

1 person in 3 1 person in 15

37.4% 6.6%

A A
B B AB AB

Rh Positive Rh Negative
Rh Positive Rh Negative Rh Positive Rh Negative

1 person in 3 1 person in 16
1 person in 12 1 person in 67 1 person in 29 1 person in 167

35.7% 6.3%
8.5% 1.5% 3.4% .6%

ABO Blood Types

Phenotype Genotype O i i A I A or I A i A I B I B I B or I B i AB IA IB

Punnett square Type A and Type B cross

IB IAIB

i
IAi

IA

IA

IAIB

IAi