Blood

Chapter 17

Review: What is Blood?• Only fluid connective tissue

– Plasma– Formed elements

• Erythrocytes (RBC’s)• Leukocytes (WBC’s)• Thrombocytes (platelets)

• Hematocrit is % of RBC’s out of total blood volume

1

2

Withdraw blood and place in tube

Centrifuge

Plasma(55% of whole blood)

Formed elements

Buffy coat:leukocyctes and platelets(<1% of whole blood)

Erythrocytes(45% of whole blood) Figure 17.1

Physical Characteristics

• pH 7.35 – 7.45• Temperature about 38°C (normal 37°C)• Approximately 8% body weight

• Males: 5 – 6 L• Females: 4 – 5 L

• Human blood is NEVER blue– Scarlet (oxygen-rich)– Dark red (oxygen-poor)

Functions

• Distribution– O2 and nutrients in

– CO2 and wastes out – Hormones to target cells

• Regulation– Body temp

• Absorb/distribute heat

– pH• Buffer systems• Bicarbonate atoms

– Fluid volumes• Salts and proteins

• Protection– Prevent blood loss

• Clot formation• Platelets and proteins

– Prevent infection• Fight foreign invaders• Antibodies, WBC’s, and

complement proteins

Plasma

• 90% water• 100+ dissolved solutes– Proteins

• Albumin: osmotic pressure• Globulin: antibodies and transport proteins• Fibrinogen: role in clotting

– Nutrients: fuel from digestive tract– Electrolytes: osmotic pressure and pH– Gases: O2 and bicarbonate ions bound to hemoglobin– Hormones

Formed Elements

• ‘Cell’ types– WBC’s are complete cells– RBC’s without nuclei or organelles– Platelets are cell fragments

• Live only a few days• Don’t divide, but are renewable– Where does hematopoiesis occur?

Erythrocytes (RBC’s)

• Biconcave shape – Large SA to small volume– Flexibility to pass through vessels

• Primarily composed of hemoglobin – Readily binds/transports O2 and CO2

• Generate ATP anaerobically– Means what?– No mitochondria

Hemoglobin (Hb)

• Transports respiratory gases– Globin protein bound to 4 hemes containing iron– 1 RBC about 250 million Hb molecules = 1billion O2

• Normal values– 14-20g/100ml infants– 13-18g/100ml males– 12-16g/100ml females

• Specific types– Oxyhemoglobin– Deoxyhemoglobin– Carbaminoglobin (binds amine groups)

Hematopoiesis• Hemocytoblasts (stem cells) commit to a

formed element– Unchangeable after– Growth factors and hormones ‘push’ to specialize

• Erythropoiesis 15 days (+ 2 to mature)

• Leukopoiesis discussed later

Hormonal Control of Erythropoiesis

• Erythropoietin (EPO) release by kidneys– Decreased RBC numbers (trauma)– Decreased O2 availability (altitude)

– Increased O2 demand (exercise)– Insufficient hemoglobin (iron deficiency)

• EPO inhibited by high O2 or RBC count– Type of feedback?

• Kidney fails = no EPO = low RBC count– EPO injections

• Abuse by athletes to increase hematocrit

Erythropoiesis Homeostasis

Kidney (and liver to a smaller extent) releases erythropoietin

Imbalance

Reduces O2 levels in blood

Erythropoietin stimulates red bone marrow

Enhanced erythropoiesis increases RBC count

Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Imbalance

Start

Increases O2-carrying ability of blood

Dietary Regulation

• Iron is key– 65% stored in hemoglobin (Hb)– Free ions are toxic, so stored bound to proteins– Some lost daily

• B12 and folic acid – Necessary for DNA synthesis– Roles in mitosis

• AA’s, lipids, and carbs too

Life and Death of Erythrocytes

• 100 – 120 day– Cells age and Hb degenerates– Engulfed by macrophages

• Components of Hb separated– Heme bilirubin urobilinogen

• Bilirubin binds albumin and moves to liver• From liver with bile to intestines• Out in feces

– Iron saved and bound to protein for storage– Globin metabolized to AA’s and into circulation

• See fig. 17.7

Erythrocyte Disorders

• Anemias: low O2carrying capacity; sign not disease– Insufficient number of RBC’s

• Hemorrhagic anemia: blood loss; acute or chronic• Hemolytic anemia: lysing of RBC’s early from parasites, mismatched blood• Aplastic anemia: disruption/destruction of red bone marrow

– Low Hb content• Iron-deficiency anemia: inadequate iron intake• Pernicious anemia: deficiency of B12 in diet

– Abnormal Hb• Thalassemia: absent or faulty globin chain• Sickle-cell anemia: defective gene codes for abnormal HB

• Polycythemias: high number of RBC’s– Blood doping: remove and replace RBC’s = artificial polycythemia– Secondary polycythemia: EPO increase when O2 levels down (high

altitude)

Leukocytes

• Not confined to blood vessels• Chemotaxis to locate damage/infection• Working WBC’s increase production of WBC’s– Leukocytosis: high WBC count response to

infection• General types– Granulocytes– Agranulocytes

Granulocytes

• Characteristics– Larger and shorter-lived than RBC’s– Phagocytic cells with lobed nuclei– Cytoplasmic granules

• Types– Neutrophils: body’s 1st phagocytic cells– Eosinophils: fights parasitic worms and lessens

allergies by phagocytizing immune complexes– Basophils: release histamine, a vasodilator

Agranulocytes

• Characteristics– Spherical or kidney like nuclei

• Types– Lymphocytes• T cells: direct action against infected cells• B cells: become cells that produce antibodies

– Monocytes • Become macrophages after leaving blood supply• Active phagocytes that also activate lymphocytes

Nuclei Cytoplasm color

Neutrophils 3 – 6 lobes light purple

Lymphocytes large, circular, purple

pale blue

Monocytes U or kidney shaped; purple

pale blue

Eosinophils 2 lobes; red red/crimson

Basophils U or S shaped; purple

purple-black

Recognizing Leukocytes

Leukopoiesis

• All leukocytes originate from hemocytoblasts– Either myeloid or

lymphoid stem cell lines

• Myeloid stem cells– Myeloblasts– Monoblasts

• Lymphoid stem cells– Lymphoblasts

• Similarities to erythropoiesis

Hormonal Control of Leukopoiesis

• Interleukins – Numbered (IL – 1, IL – 2, IL – 3, etc.)

• Colony-stimulating factors (CSFs)– Named for the WBCs stimulated (granulocyte –

CSF)• Hematopoietic factors from red bone marrow

and WBCs too– Encourage maturation and division– Used clinically after chemotheraphy, stem cell

transplants, or in AIDS patients

Leukocyte Disorders

• Leukpenia: abnormal WBC count; usually drug (anticancer) induced

• Leukemia: cancerous conditions named for cell type involved– Bone marrow fills with cancerous leukocytes– Numerous, nonfunctional WBCs produced– Myelocytic (myeloblasts) or lymphocytic (lymphocytes)– Acute (blast-type cell) or chronic (later cell stage)

• Mononucleosis: epstein-barr virus; excessive agranulocytes

Platelets• Fragments of megakaryocytes

– Myeloid stem cell line– Mitotic without cytokinesis

• Anucleate, live about 10 days– Thin blue cytoplasm with a few purple granules

• Form temporary plugs during the clotting process• Thrombopoietin regulates their production

Hemostasis• Stoppage of bleeding

– Platelets, clotting factors, and injured tissues involved• 3 phases

– Vascular spasm• Rapid vasoconstriction of damaged vessel• Efficiency increase with damage

– Plug formation• Platelets bind to exposed collagen in damaged vessel• Positive feedback of chemical messengers to attract more platelets

– Coagulation • Liquid to gel• Endothelial cells (extrinsic) and platelets (intrinsic) factors interact with clotting

factors

• Fibrous tissue eventually regrows to permanently seal

Coagulation Process• Phase One: prothrombin activator pathways

– Intrinsic: factors in blood already • Slower b/c many steps

– Extrinsic: tissue factor III (TFIII) outside blood in tissue• Faster b/c skips steps

• Phase Two: thrombin activation– Prothrombin activator catalyzes– Prothrombin protein to thrombin enzyme

• Phase Three: fibrin mesh produced– Fibrinogen catalyzed to fibrin– Fibrin glues platelets together = clot

• Plasma becomes gel-like

– Factor XIII strengthens, sealing fibrin together• Fig 17.14 http://www.astrographics.com/cgi-bin/ase/

ase.cgi?affiliate=sciam&mode=display&gallery=3&type=medical&color=&keywords=&page=2

Clot Retraction and Repair

• Contractile proteins of proteins pull fibrin strands together– Stabilizes clot

• Platelet derived growth factor (PDGF) stimulates smooth muscle and fibroblast mitosis to rebuild wall

• Fibrinolysis dissolves clots– Beneficial once healed– Prevents build up in vessels

Controlling Clot Formation

• Limit growth through constant blood circulation– Keeps [clotting factors] low in given locations

• Inhibit thrombin (intrinsic pathway too)– Fibrin binds to prevent spread– Antithrombin III (in plasma) inactivates – Heparin enhances antithrombin III and inhibits pathway

• Prevent clotting– Antithrombics (NO) and undamaged vessel tissue

prevents platelet adhesion– Blood thinner administration (aspirin, warfarin)

Hemostasis Disorders (Thromboembolytic)

• Undesirable clot formation• Thrombus: clot in an unbroken blood vessel– Can block normal blood flow = tissue death– Coronary thrombus may cause heart attack

• Embolus: free floating clot– Embolism once blood vessel is obstructed– Pulmonary embolisms inhibit obtaining O2– Cerebral embolisms may cause strokes

Hemostasis Disorders (Bleeding)

• Problems controlling bleeding• Thrombocytopenia: platelet number is low– Spontaneous bleeding all over body from mov’t

• Purple blotches on skin signify

• Liver can’t produce procoagulants– Vitamin K deficiencies– Other liver diseases

• Hemophilia: genetic disorder causing missing clotting factors– Type depends on affected factor

Human Blood Groups

• RBC membranes have glycoprotein antigens on external surface– Unique to individuals– Recognized as foreign by other individual bodies– Agglutinogens because they promote

agglutination (clumping)• Presence or absence of antigens used to

classify blood groups

ABO Blood Groups• Two antigens (A and B) on RBC surface in blood

– Blood types: A, B, AB, and O• Two antibodies (anti-A and anti-B) in the plasma

– Non-complement to blood type produced– See chart below

• Agglutinogens and complement antibodies can’t mix w/o hemolytic reaction

• Newborns don’t start development until 2 months after birth; complete between 8 and 10

Blood Type Antigen A Antigen B Antibody anti-A Antibody anti-B Receive ?

A Yes No No Yes

B No Yes Yes No

O No No Yes Yes

AB Yes Yes No No

Rhesus (Rh) Blood Groups• Multiple agglutinogens– C, D, and E most common– Named for monkey first discovered in

• Rh+ individuals have the D antigen– Lack anti-Rh antibodies produced in plasma– Can receive Rh+ or Rh- blood

• Rh- individuals lack the D antigen– Lack anti-Rh, but can produce w/ Rh+ transfusion

• 1st occurrence = sensitization (no reaction), starts production

• 2nd occurrence+ = attack and lysis of donor RBC’s

Transfusions Gone Wrong

• Transfusion reactions when mismatched blood is exchanged– Recipient's plasma attacks donor’s RBC’s• Donor’s plasma may attack recipient’s RBC’s, but less

serious condition

– RBC’s hemolyse or phagocytize

• O2 carrying capacity drops• Agglutination clogs small vessels• Hb released into blood kidney damage

possible

Diagnostic Blood Tests

• Hematocrit: % of RBC in blood• Differential WBC count: different number of

WBC cells• Platelet count: ability of blood to clot• Complete blood count (CBC): number of

formed elements, hematocrit, Hb, and RBC size

• Hemoglobin: amount in blood