Chapter 19 - Blood

What is Blood

• specialized fluid of connective tissue containing cells suspended in fluid matrix

Physical Characteristics of Blood

Normal Temp: 38^oC (100.4^oF)

• High viscosity

• Slightly alkaline pH (7.35-7.45)

Major Functions of Blood

• transport system

  • O2, CO2, nutrients, hormones, waste, cells

• regulation of pH & ion concentration

• restriction of fluid loss at injury sits (hemostasis)

• defense against toxins & pathogens

• stabilizing body temp

Make Up of Whole Blood

Plasma

• water, plasma proteins (made by liver), other solutes

• 55%

Formed Elements

• RBC, WBC, platelets (pieces of cells), other solids

• 45%

Plasma Make Up

Plasma Proteins (7%)

• albumins

• globulins

• firbrinogen

Other Solutes (1%)

• specialized plasma proteins

  • i.e. antibodies, complement proteins

• quantities vary

Water (92%)

Albumins

• 60%

• produced in liver

• transport fatty acids & hormones

Globulins

• 35%

• antibodies (aka immunoglobulins)

• transport globulins for hormones & steriods

Fibrinogen

• 4%

• involved in blood clotting process, forming insoluble strands of fibrin from dissolved fibrinogen in serum

  • serum is plasma w/o antibodies

Other Plasma Proteins

• 1%

• specialized proteins present at varying levels

  • ex: peptide hormones (insulin, follicle-stimulating hormone)

Types of Formed Elements

Red Blood Cells / Erythrocytes

• transports ocygen

White Blood Cells / Leukocytes

• component of immune system

Platelets

• cell fragments involved in clotting

Hemopoiesis

• process of producing formed elements stimulated by erythropoietin (EOP)

  • EOP released by kidney

• produced from hematopoietic stem cells in bone marrow

• generates ~3 mil new RBCs per sec

Red Blood Cells

• small, highly specialized discs comprising 99.9% of formed elements

• contains hemoglobin, which transports O2 & CO2

  • provides red color

• 1% die out per day

Red Blood Cell Count

• # of RBCs in 1microliter of whole blood

• Males — 4.5-6.3 million

• Females — 4.2-5.5 million

Packed Cell Volume (PCV)

% of formed elements in centrifuged whole blood

Hematocrit

% of RBC in centrifuged whole blood

Structure & Function of RBCs

• high surface-to-volume ratio to exchange O2 rapidly

• flexbility to transverse small capillaries

Life Span of RBCs

• lack nuclei, mitochondria, ribosomes

• unable to divide for synthesis of proteins

• no repair mechanisms

• only anaerobic metabolism

• 120 days

Rouleaux

stacks formed by discs

Hemoglobin (Hb)

• molecule with 4 globular protein subunits that transport respiratory gases

  • each subunit contain one molecule of heme

  • each heme contains free Fe²⁺ ion (contributes to red color) that binds O2

  • Hb + O₂ = HbO₂ (Oxyhenoglobin)

  • HbO₂ - O₂ = Deoxyhemoglobin

• each subunit carries O₂

Fetal Hemoglobin

• potent form of Hb present in developing fetus

• can take O2 from mother’s Hb

Carbaminohemoglobin

Hemoglobin containing CO₂

• low O₂ state (e.g. at peripheral capillaries), Hb releases O₂ & binds CO₂

• carries CO₂ to lungs

• CO₂ doesn’t bind to heme

RBC Turnover

• macrophages of liver, spleen, bone marrow monitor RBC population & engulfs RBCs before membrane ruptures or hemolyzes

• phagocytes break down Hb complex

  • proteins converted to AA

Hemoglobinuria

hemoglobin in urine due to excess hemolysis in bloodstream

Hematuria

whole RBCs found in urine due to kidney or tissue damage

Breakdown Of Heme

• heme is metabolized into biliverdin by removal of iron

• biliverdin (green) is quickly metabolized to bilirubin

• bilirubin (yellowish-orange) is excreted by liver through bile

  • buildup of bilirubin causes jaundice

  • bilirubin is converted to urobilins & stercobilins by intestinal bacteria

Fe²⁺ Recycling

• Fe²⁺ is released by metabolism of heme

• Fe²⁺ is either transported or stored

  • transported by transferrin

  • stored by forming complex with ferritin or hemosiderin

Erythropoiesis

• in adults, erythropoiesis occurs only in myeloid tissue (red bone marrow)

• generation of RBCs requires amino acids, Fe²⁺, Vit B_12, Vit B₆, folic acid

• EPO secreted from kidney when O₂ in peripheral tissues is low

Hemocytoblasts

stem cells

• erythroid stem cells → RBCs

• myeloid stem cells → WBCs

• lymphoid stem cells → Lymphocytes

Hypoxia

low O2

Anemia

condition resulting from low hematocrit or Hb content

Pernicious Anemia

low RBC production due to lack of Vit B₁₂

Blood Doping

dangerous practice by athletes to elevate hematocrit

Erythropoiesis: Stages of RBC Maturation

Myeloid Stem Cell

Proerythroblast

Erythroblast

Reticulocyte

Mature RBC

Blood Typing

• determined by presence or absence of surface antigen on RBCs

• blood type genetically determined by A, B, Rh antigens

• surface-expressed antigens are “screened” by immune system

• circulating anti-antigen antibodies bind “forgein” antigens

Type A Blood

Surface Antigen: Antigen A

Anti-Antigen Antibodies: Anti-Antigen B Antibodies

Type B Blood

Surface Antigen: Antigen B

Anti-Antigen Antibodies: Anti-Antigen A Antibodies

Type AB Blood

Surface Antigen: Antigen A & B

Anti-Antigen Antibodies: NO Anti-Antigen A or B Antibodies

Type O Blood

Surface Antigen: NO Antigen A or B

Anti-Antigen Antibodies: BOTH Anti-Antigen A & B Antibodies

Rh Factor (Antigen D)

Rh⁺ → antigen D

Rh^-- → no antigen D

Agglutination

binding causes clumping of foreign antigens

Agglutinogens

RBC surface antigen antibodies

Rh Factor & Pregnancy

• humans are either Rh⁺ or Rh^-

• only sensitized Rh- blood has anti-Rh antibodies

• since fetal blood does not typically mix with maternal circulation, mother is not exposed to Rh factor

  • Rh^- mother’s blood does not express anti-Rh antibodies

Hemolytic Disease of Newborns

• next time mother is pregnant, anti-Rh antibodies from maternal blood can enter fetal circulation

• anti-Rh antibodies will bind to Rh+ fetal RBC & cause hemolysis

• treat mother with anti-Rh antibodies (RhoGAM) to prevent sensitization

Blood Transfusion

• blood must be tested for compatibility

• is transfused blood is not compatible, plasma antibodies will recognize its specific antigen

• blood cells will agglutinate

• results in hemolysis of RBCs

Transfusion Reaction

plasma antibodies recognize specific surface antigen

Cross-Matching

critical to check compatibility of donor & recipient

Type O^-

• universal donor

• no surface antigen on RBCs (type O)

  • no Rh factor (negative)

Type AB^-

• universal recipient

• both surface antigens on RBCs (type AB)

  • no Rh factor (negative)

Proerythroblast

large cells with large nucleus surrounded by small amount of cytoplasm

Megakaryocyte

• precursors of platelets

• found in bone marrow

Platelets

• aka thrombocytes

• cell fragments involved in clotting system

• circulate for 9-12 days

• removed by phagocytes in spleen

Thrombocytopenia

low platelet count

Thrombocytosis

high platelet count

Functions of Platelets

• release clotting chemicals

• temporarily patch damaged vessel wall

• reduced size of break in vessel wall

Thrombocytepoeisis

formation of platelets from cytoplasm of megakaryocytes in bone marrow

Hormones Involved in Platelet Production

• thrombopoietin

• interleikin-6 (IL-6)

• multi-colony stimulating factor (Multi-CSF)

Hemostasis

cessation of bleeding

Phase 1 of Hemostasis

Vascular Phase

• cut triggers vascular spasm that lasts 30 min

• endothelial cells release factors in response

• tissue factor, prostacyclin, ADP

• Endothelins

  • stimulate smooth muscle contraction & endothelial division

• cells become sticky & act to seal off blood flow

Phase 2 of Hemostasis

Platelet Phase

• begins within 15 sec of injury

• platelets stick to endothelial cells, basement membranes, exposed collagen fibers

• aggregate to plug break

• release clotting compounds

• ADP - platelet aggregation

• thromboxane A2

• serotonin - vascular spasm

• clotting factors

• PDGF - vessel repair

• calcium - clotting factor

Factors that Limit Platelet Plug Size

• Prostacyclin & Nitric Oxide - inhibit aggregation

• inhibitory factors are released by other WBCs

• ADP breakdown inhibits platelet aggregation

• negative serotonergic feedback to reduce release of serotonin

• clot isolates injured area

Phase 3 of Hemostasis

Coagulation Phase

• blood clotting begins in less than 30 sec after injury

• enzymatic chain reactions convert circulating fibrinogen into insoluble fibrin

• Ca²⁺ & Vit K

  • all pathway require Ca²⁺

  • Vit K needed for synthesis of 4 clotting factors

Extrinsic Pathway

• begins in vessel wall, outside bloodstream

• damaged cells release tissue factor (TF)

• TF & other factors form enzyme complex activates Factor X

Intrinsic Pathway

• begins with circulating proenzymes, within bloodstream

• enzymes form prothrombin activator complex that converts prothrombin → thrombin

• thrombin converts fibrinogen → fibrin

Regulation of Clotting

• pathways regulated by positive & negative feedback loops

• to accelerate clotting, increase production of TF or Platelet Factor-3 (PF-3)

• to inhibit clotting, increase production of anticoagulants

Examples of Anticoagulants

Antithrombin-III - inhibits thrombin

Heparin - released by mast cells

• activates antithrombin-III

Aspirin

Protein C - activated by thrombomodulin

• stimulates formation of plasmin

Prostacyclin - vasodilator

• opposes thrombin activity

Hemophilia

inherited bleeding disorder

Thrombophilia

increased clot formation

• Deep Vein Thrombosis (DVT) - clots form in venous system

• Pulmonary Embolism - moving clot blocks one of vessels of lung

Phase 4 of Hemostasis

Clot Retraction

• pulls torn edges of vessel closer together

• reduces residual bleeding

• stabilized injury site

• reduces size of damaged area

• fibrinolysis - slow dissolving clot

  • thrombonin & tissue plasminogen activator (t-PA) convert plasminogen to plasmin

• plasmin digests fibrin strands & dissolves clot