BLOOD

Blood

• fluid connective tissue • contains specialized cells-

formed elements

• suspended in matrix-

plasma

• containing-collagen & elastic fibers –protein fibers are in solution-visible during clotting process

Functions

•

transports

&

distributes

nutrients, gases, hormones & waste products • regulates

pH & ion

interstitial fluids composition of • restricts

fluid loss

at injury sites •

defends

against toxins & pathogens • helps to maintain

body temperature

• • •

Composition

• 8% of total body weight –5-6 liters in males –4-5L in females

Temperature-

38

o

C –just above body temperature

Viscosity

5X more viscous than water

pH

between 7.35-7.45

Composition

•

Whole blood =

formed elements plasma + • red blood cells (

RBCs)

• white blood cells • platelets

(WBCs)

• Centrifuged-separates into three parts • Bottom-

erythrocytes

(

RBCs) • top-

plasma

• junction of RBC & plasma-

buffy coat

– contains WBCs &

platelets

Plasma Composition

• • • • 46-63% of blood volume • 92% water • plasma proteins-made by liver

Albumin

-60% – major contributor to osmotic pressure – transports fatty acids, steroid & thyroid hormones

Globulins-

lipids 35% – from smallest to largest in molecular weights-alpha, beta & gamma globulins – used to transport hormones, metal ions, triglycerides and – includes

antibodies

or immunoglobins • defend against infections and foreign materials

Fibrinogen-

4% – blood clotting – fibrinogen is cleaved into

fibrin-

basic framework of clot

• • • • •

Erythrocytes

most numerous of formed elements number varies with health & altitude – Peruvians who live 18,000 feet above sea level may have as many as 8.3 x 106 RBCs/µl contain hemoblobin (Hb) – red pigment which transports O 2 – gives blood its color & CO 2 Ratio of RBC/plasma is (

PCV)

hematocrit

– % of whole blood occupied by cellular elements: 40-45%-women; 37-48%-men – almost entirely due to volume of RBCs – provides estimate of packed cell volume – PCV increases with dehydration & with erythropoietin-protein which stimulates RBC production RBCs are a major contributor to blood viscosity – as numbers increase  viscosity increases  blood flow slows  blood thins  flows more rapidly

• • • • • • • • •

RBC Structure

simple-small,

biconcave

disc plasma membrane-no nucleus & no organelles

bag of Hb

no nucleus days  cannot divide or make proteins – can’t repair its self and has a short life span-120

shape

is directly related to function-most important transport of O 2 – large surface area, relative to volume – 30% more surface area than spherical cells – larger surface area makes for faster gas exchange shape allows them to stack like dinner plates – allows for

smoother

flow of blood through vessels Flexible – able to pass through small capillaries Modify shape in response to osmotic changes – Hypotonic solution  – Hypertonic solution  swells  shrinks forms sphere without disrupting integrity of membrane  forms spikey surface No mitochondria – generate ATP

anaerobically

via glycolysis – do not need O 2 - makes them very efficient O 2 transporters

Hemoglobin (HB) Structure

• red pigment • formed by 4 globular polypeptide chains • 2  & 2  • each chain has a molecule of heme • each heme has iron (Fe) molecule • each Fe can carry one molecule of oxygen oxygen  therefore each HB molecule can carry 4 molecules of • Fe binds with O 2 

oxyhemoglobin

 bright red • Fe-O 2 bond is weak • can separate easily without damage to Fe or O 2 • Hb from which O 2 has separated is

deoxyhemoglobin

 dark red

• •

Hemoglobin Functions

Transport gases-O 2 CO 2

–

there are 280X106 Hb molecules in each RBC &

–

each contain 4 heme groups

–

gives blood capacity to carry a billion O 2 molecules amount of O 2 bound depends on O 2 content of plasma

Leukocytes-White Blood Cells

• • • less numerous than RBCS • 1% of total blood volume • provide protection against infections •

complete cells

– typically have lobed nuclei, organelles & no Hb • two groups based on appearance after staining

Granulocytes

– contain cytoplasmic inclusions –

Basophils

– –

Eosinophils Neutrophils

Agranulocytes

– contain only a very few stained granules – –

Lymphocytes Monocytes

• • • • • • • • • • • • • • •

Neutrophils

60-70% of circulating WBC population live only about 10 hours twice size of RBC Nucleus-

polymorphonuclear

– varied nuclear shapes – mature have 3-5 lobes connected by slender nuclear strands cytoplasmic granules in cytoplasm are packed with lysosomal enzymes & bacteria killing compounds produced in response to

acute body stress

– infection, infarction, trauma, emotional distress can double in a few hours highly mobile – first WBC to arrive at injury site specialize in attacking & digesting bacteria when binds to bacterium  metabolic rate increases  H 2 O 2 -hydrogen peroxide & O 2 - superoxide anions are produced which kill bacteria neutrophil + bacterium will fuse with a l

ysosome

contains digestive enzymes &

defensins

which defensins kill bacteria & lysozymes digest them makes prostaglandins & leukotrienes during this process – restricts spread of infection & attracts other phagocytotic cells cell kills its self in the process Neutrophils + other waste =

pus

Eosinophils

• 2-4% of WBCs • bilobed nuclei • contain

deep red

granules • population increases sharply during

parasitic

infections & allergic responses • release histaminases which combat the effects of histamine

• 0.5-1%

Basophils

• smallest part of WBC population • large, deep purple granules in cytoplasm – hides nucleus • increase in number during infections • leave blood & develop into mast cells • granules contain

histamine, serotonin & heparin

• histamine increases blood flow to area which dilates blood vessels

heparin

prevents blood clotting

Monocytes

• largest agranulocytes • 3-8% of WBC population • nucleus is large – clearly visible – ovoid or kidney shaped • cytoplasm contains sparse, fine granules • arrive in large numbers at the site of an infection • enlarge & differentiate into wandering macrophages

Lymphocytes

• second most numerous circulating leukocyte 25-33% • Nucleus-large, round or slightly dimpled on one side • continually migrates from blood stream through peripheral tissues & back to blood stream • life span varies from several days to years •

B cells or B lymphocytes

– bone marrow derived – make antibodies which attack foreign antigens •

T lymphocytes

or T cells –

thymus dependent

cells – provide cell mediated immunity – attack foreign cells •

Natural Killer Cells

–

immune surveillance cells

–

detect &destroy abnormal tissue cells

–

may help prevent cancer

Differential Cell Count

• determines number of each type of WBC in a sample • gives valuable information • pathogens, infections, inflammation & allergic reactions change WBC numbers • count of different types can help to diagnose disease and illness • Leukopenia – inadequate number • Leuocytosis – Excessive number

Blood Cell Formation

• all formed elements arise from a single cell type:

pluripotent stem cell

•

Hemocytoblast

•

hematopoietic stem cell

or

hemocytoblast

• rare-one in 10,000 bone marrow cells • cell differentiates along maturation path which leads to different kinds of blood cells • each type produced in different numbers in response to

needs

&

regulatory factors

-cytokines or hormones

Hemopoietic Tissues

• Tissues producing blood cells • first-yolk sac – makes stem cells that migrate into embryo thymus • Liver • Spleen onward  time of birth  populate bone marrow, liver, spleen & stem cells multiply & give rise to blood cells throughout fetal development – primary site of RBC production during 2-5th month neonatally is liver & spleen – stops making blood cells at – stops soon after but continues to make white blood cells throughout life • red bone marrow produces all formed elements from infancy

Erythropoiesis

• inadequate oxygen (hypoxia)  kidney  stimulates production of RBCs EPO (erythopoietin)  • Hemoblasts  myeloid stem cells  proethryoblast  early erythroblasts • early erhtyhroblasts multiply & make hemoglobin  late erythroblast  normoblast • once normoblast accoulates 34% Hb  organelles are ejected, nucleus degenerates  cell collapses inward  reticulocyte • still has ribosomes & rough ER; leaves bone marrow • matures in two days  mature erythrocyte

• • • • • • • • • • • • • •

RBC LifeCycle

RBC is

terminally differentiated

cannot synthesize proteins, enzymes or renew membranes life span-about 120 days engulfed & destroyed by phagocytotic cells in liver, spleen and bone marrow process is

hemolysis

once hemolyzed-parts are broken down globular proteins are disassembled into amino acids

Heme splits

from

globin

of

HB molecule

Iron is stripped from heme 

biliverdin

(green, organic compound)  bilirubin (orange/yellow pigment)  released into blood  binds albumin  transported to liver for excretion in bile – If circulating levels cannot be handled by liver  yellow

hyperbilirubinemia-

 jaundice condition which turns peripheral tissues Fe salvaged for reuse toxic to body-must be stored & transported bound to a protein Tranferrin used for iron transport hemosiderin for iron storage in bone marrow Fe is taken into the mitochondria of developing RBCs and is used to make heme

WBC Production-Leukopoiesis

• • • • begins with same pluripotent stem used in erythropoiesis hemocytoblast • differentiate into distinct types of CFUs-colony forming units • CFUs go on to produce 3 cell lines committed to a certain outcome

Myleoblasts Monoblasts Lymphoblasts

Leukopoiesis

• • • • • • •

Platelets-Thrombocytes

not cells in strictest sense – Fragments continuously replaced always present-not active unless damage has occurred Thrombocytosis – too many Throbocytopenia – Too few if numbers drop below 50 X 10 3 /ul there is danger of uncontrolled bleeding Functions – contain chemicals for clotting – form temporary platelet plug needed in clotting – secrete growth factors – secrete chemical to attract neutrophils and monocytes to site of inflammation

Thrombocytopoiesis

• occurs in bone marrow • thrombopoieten-secreted by liver  stimulate growth & maturation of hemocytoblasts  repeated mitosis (up to 7X) without nuclear or cytoplasmic division  very large polypoloid cell-megakaryocyte • presses against sinusoid wall  rupture  platelet fragments • life span-about 5 – 9 days

Hemostasis

• cut or damaged blood vessels bleed • outflow must be stopped before shock & death occur • accomplished by solidification of blood or coagulation • also called clotting or hemostasis • clotting is • fast • localized • carefully controlled • three phases – vascular spasm – platelet plug formation – coagulation phase

Vascular Spasm Phase • blood vessels vasoconstrict –diameter decreases at injury site • immediate & most effective in small vessels • contraction exposes underlying basement membrane to bloodstream

• • • • • • • •

Platelet Plug Formation

endothelial cell membranes become sticky sticky membranes allow platelets to adhere to injury site forms temporary plug within 1 minute of injury as platelets keep arriving continue sticking to each other  platelet aggregation  platelet plug plug seals break in vessel as arrive become activated  change shape become more spherical & develop cytoplasmic processes that extend toward other platelets Release – ADP-adenosine diphosphate • aggregating agent – Serotonin • enhances vascular spasms – Enzymes that help make Thromboxane A2 • recruits & activates more platelets & stimulates vascular spasms – PDGF • platelet derived growth factor • promotes vessel repair – Calcium • required for platelet aggregation

Coagulation Phase

• occurs in asequence of steps • requires 13 clotting factors called procoagulants • designated by Roman numerals – many circulate as proenzymes- inactive precursors • converted to active forms during clotting process • activated by proteolytic cleavage & active proteases • all but 3 are made & released by the liver (III, IV, VIII) • all but 2 (III & VIII) are always present in blood • activated platelets release 5 during platelet phase (III, IV, V, VIII & XIII )

Coagulation Cascade

• activation of one proenzyme  activates another proenzyme • chain reaction or reaction cascade • 2 reaction pathways to coagulation: • extrinsic • Intrinsic • Both lead to the formation of prothrombinase • at this point the two unite common pathway

Extrinsic Pathway

• shorter & faster-fewer steps • TF-tissue factor or thromboplastin or clotting factor III is released by damaged blood vessels • leaks into blood (extrinsic to it) • TF binds Ca complex ++ & Factor VII forming an enzyme • complex cleaves Factor X (prothrombinase)  active factor X • first step in common pathway of coagulation

Intrinsic Pathway

• more complex & slower • activators are in blood or in direct contact with it (intrinsic to it) • contact with collagen fibers or even glass of a collecting vial  activates Factor XII • Begins a series of reactions • activated factors VIII & IX combine to form enzyme complex which activates Factor X

Common Coagulation Pathway

• the two paths unite at a common pathway  thrombin synthesis • begins when activated Factor X or prothombinase converts prothombin or Factor II  thrombin • Thrombin cleaves fibrinogen or Factor I (soluble)  insoluble fibrin

The Clot

• fibrin glues platelets together forming intertwined web – structural basis of a clot • thrombin & Ca ++ activate Factor XIII-fibrin stabilizing factor • cross linking enzyme • forms covalent bonds between fibrin molecules converting them into insoluble meshwork • stabilizes clot

Clot Retraction

• further stabilizes clot • occurs minutes after initial clot formation • platelets contain contractile proteins-actin & myosin • these contract  pull fibrin strands together • squeezing out serum  compacts clot • functions to: • pull torn edges of broken vessel together • reduce size of damaged area

Rebuilding

• begins with clot formation • PDGF  stimulates smooth muscle cells & fibroblast division to rebuild vessel wall – angiogenesis • Thrombin, factors VII & X promote healing by stimulating growth of new blood vessels at site of damage

Fibrinolysis

• hemostasis is not complete until clot has been dissolved • plasminogen is incorporated into clot as it forms • nearby cells release TPA-tissue pasminogen activator • binds to fibren and activates plasimnogen converting it to plasmin • plasmin  digests fibrin  dissolving clot

Control of Clotting

• clotting must be carefully regulated • inappropriate formation life-threatening – too much-thrombus • clotting-restricted by several mechanisms • 1. Platelets do not adhere to normal endothelium – intact endothelial cells convert membrane lipids into prostacyclin • blocks platelet adhesion & aggregation • limits platelet plug to area of damage

Control of Clotting

• Plasma contains anticoagulants – Antithrombin III inactivates thrombin – Heparin accelerates activation of antithrombin III  enhances inhibition of thrombin synthesis

Control of Clotting

• 3. Endothelial cells release thrombomodulin-binds to thrombin  converts it into enzyme that activates protein c • Protein C  inactivates clotting factors & stimulates plasmin formation

Thromboembolytic Disorders

• Undesirable clotting  circulation thrombus – blood clots in unbroken vessels • gets into coronary  & floats free heart attack • thrombus that breaks away  embolus • Cerebral embolus  stroke • Pulmonary embolus formation – Arteriosclerosis  lung • Conditions that roughen endothelium encourage clot

• • • • •

Bleeding Disorders

Thrombocytopenia – deficient platelet number – can result in spontaneous bleeding from small vessels Impaired liver function – liver makes procoagulants & when unable to do so result is severe bleeding Deficiency of Vitamin K – may be a cause of liver dysfunction – cofactor needed for synthesis of factors II, VII, IX, X & proteins C & S – blocking action of vitamin K helps prevent inappropriate clotting • Warfarin-vitamin K antagonist Deficiency of clotting factors – not enough produced or mutant version fails to perform properly – von Willebrand disease-most common – Hemophilia A-classic-factor VIII deficiency – antihemophilic factor-hemophilia B – factor XI deficiency-hemophilia C – actor XI deficiency-in both sexes Lowered Calcium – affects nearly all clotting pathways – any lowering of Ca impairs blood clotting

Hemophilia Inheritance

ABO Blood Types

• blood type-determined by presence or absence of antigens-A and B • Presence of A-blood type A • Presence of B-blood type B • Presense of both-blood type AB • Absence of both-blood type O

ABO Blood Types

• antibodies begin to appear in plasma 2 to 8 months after birth • person produces antibodies against antigens that are

not present

on his or her RBCs • Blood type A-makes antibody B • Blood type B-makes antibody A • Blood type O-makes antibodies A & B • Blood type AB-does not make antibodies

Blood Type

• Antigens are often referred to as

agglutinogens

•

Antibodies-

immunoglobulins are made by immune system in response to foreign material-agglutinins • antibody adheres to foreign material & eliminates it • presence of antigens on cells is a way for immune system to decide whether substance is foreign or not • immune system ignores surface antigens on your RBCs • when blood-type antigen senses foreign antigen has entered system  alerts immune system to create antibodies to that antigen – antibodies attach themselves to foreign antigens  destroy them • when attack foreign cells  clump together-

agglutinate-

termed agglutination

• • • • • • •

Agglutination

Antibodies react against A or B antigen except those of one’s own RBCs person with antigen A produces anti-B antibodies  attack type B antigens person with antigen B produces anti-A antibodies  attack type A antigens person with neither A or B antigens produces both anti-A & anti-B antibodies person with both antigens A & B will produce no antibodies When antibody meets specific surface antigen  RBCs agglutinate & may hemolyze – Cross reaction or transfusion reaction – can be dangerous to receive wrong blood type during a transfusion Compatibility can be verified with

antiserum

antiserum

blood typing

– mix small sample of blood with anti-A or anti-B antibodies-called – presence or absence of clumping is determined for each type of – clumping only with anti-A serum  blood type A – clumping only with anti-B serum  blood type B – clumping with both antigens  blood type AB – Absence of clumping with either antigen  blood type O

Universal Donor & Recipient • Type O-

universal donor

–no surface antigens



recipient’s blood can have antibodies but there will be no clumping • Type AB-

universal receiver

–holds no antibodies to react with antigens

Antigen D-Rh Factor

•

rhesus antigen

• in Rh negative individuals D antigen is missing • 84% of humans are Rh positive • Blood Type A+ carries A & Rh antigens • shouldn't mix A+ with A- blood • blood must also be typed for Rh factor • Anti-D antibodies are not normally found in blood as anti a and b antibodies are • form only in Rh negative individuals who are exposed to Rh positive blood • Rh negative person receives Rh positive transfusion  recipient produces anti-d antibodies • Anti-d does not appear instantaneously • presents little danger • if person gets another Rh positive transfusion, his or her anti-D could agglutinate donor’s RBCs