Circulatory Circulatory SystemSystem

-Cardiovascular & -Cardiovascular & Lymphatics-Lymphatics-

Chapters 17 - 19Chapters 17 - 19

Chapter 17 - BLOODChapter 17 - BLOOD ComponentsComponents

Only fluid connective tissue Formed elements – living cells Fluid matrix – plasma Spun tube – 45% RBC’s, 1% buffy coat (WBC’s, Platelets), 55% plasma

CharacteristicsSaltyAlkaline (7.35 – 7.45 pH)Varied in color due to O2 content

5-6 L in males; 4-5 L in females

8% of body weight

Functions (transportation Functions (transportation &/or protection)&/or protection) Distribution

O2 and food nutrientsWastes to lungs & kidneysHormones from endocrine glands to target organs

Maintains body temperature (absorbs & distributes body heat)

ProtectionMaintains pH (reservoir for bicarbonate ions)

Maintains fluid volumePrevents blood loss (through platelet action & blood proteins)

Prevents infection (through WBC’s & antibodies)

Formed Elements Erythrocytes (RBC’s)

CharacteristicsLacks nucleus & organelles – “bag of hemoglobin molecules”; 33% of RBC is hemoglobin

~ 8 m in diameter; look like flat discs with depressed centers

Shape provides large surface area ideal O2 transport

Flexible due to spectrin (fibrous protein) which allows Rouleaux movement (stacking) when traveling through capillaries

800:1 RBC’s : WBC’s = blood viscosity

4.3 – 5.2 million cells/cc RBC count in women

5.1 – 5.8 million RBC count in men

Number of cells correlates with viscosity; more RBC’s = more viscous blood = slower moving

FunctionCarry O2 through their contained hemoglobinHemoglobin consists of “globin” protein bound to red “heme” iron pigment

Each hemoglobin contains 4 ringlike heme groups

Each globin protein consists of 4 polypeptide chains; each chain is bound to a heme group

Each iron atom can combine with one O2

Thus each hemoglobin can carry 4 O2’s

Each RBC contains 250 million hemoglobin molecules = transporting 1 billion O2’s.

Also carries CO2 on the globin so there is no competition for binding sites~ 20% of CO2 is carried this way

Production of RBC’sIn red bone marrow of long & flat bones

Arise from stem cells “Hemocytoblasts” which reside in bone marrow

Hemocytoblast is transformed into a proerythroblast

Proerythroblast give rise to early erythroblast (produce large amounts of ribosomes)

Early erythroblast transforms into late erythroblast as hemoglobin production increases

Late erythroblast transforms into normoblast when hemoglobin content reaches 34%

Nucleus ceases functions & is ejected causing the center of cell collapse (thus the depressed center or disc shape)

Normoblast transforms into reticulocyte (named for remaining rough ER)

Up to this point takes 3-5 days

Reticulocytes enter circulation & become mature erythrocytes in ~ 2 days.

Process is balanced between production & destruction (about 2 million/sec) under hormonal control & with adequate amounts of iron & B vitamins.

Hormonal ControlHormonal ControlRBC production is directly linked to erythrocyte hormone (which is in system at low levels all the time to maintain production as basal levels)

Erythropoietin hormone is produced when kidney cells release REF (renal erythropoietin factor) in response to cell hypoxia. Hypoxia is due toDeclining # of RBC’s due to hemorrhaging or excessive RBC destruction

Reduced availability of O2 due to altitude or pneumonia

Increased O2 demands by tissues during exercise

It’s not the number of cells that controls erythropoietin, but the cell’s ability to transport O2

Erythropoietin stimulate red marrow to MATURE already committed cells at a faster rate than otherwise (1-2 days faster)

Testosterone can stimulate kidneys to release REF (accounting for high RBC levels in men than women; conversely those with kidney failure have RBC counts less than half of normal individuals

Dietary needs for erythropoietin productionNeed carbs, proteins, lipids, iron B-complex vitamins

65% of body’s iron supply is in hemoglobin, the rest is stored in liver, spleen and marrow (because free iron is toxic to tissues) as ferritin, hemosiderin, or transferrin

Iron loss is 1.7 mg and 0.9 mg per day in women and men respectively

B-12 and folic acid are needed for DNA synthesis in immature RBC’s

Destruction of RBC’sDestruction of RBC’sBecause they are anucleate, Because they are anucleate, they cannot synthesize they cannot synthesize proteins, reproduce, grow, proteins, reproduce, grow, etc.etc.

Lifespan of 100-120 daysLifespan of 100-120 daysDying cells become trapped Dying cells become trapped in capillaries of spleen and in capillaries of spleen and are engulfed by roaming are engulfed by roaming phagocytesphagocytes

Hemoglobin is degraded into billirubin and secreted in the bile by the liver

Released iron is salvaged and recycled

Disorders (anemias or polycythemia)Anemias – reduced O2 carrying ability of blood (really a symptom rather than a disease)Hemorrhagic anemia – results from blood loss; corrected by blood replacement

Hemolytic anemiaHemolytic anemia – – erythrocytes are ruptured prematurely (hemoglobin abnormalities, blood mismatch, bacterial or parasitic infection, congenital defects in plasma membrane)

Aplastic anemia – destruction or inhibition of red marrow (cancer and the drugs used to treat cancer can cause marrow to be replaced by connective tissue); blood transfusions are used until a bone marrow transplant can be performed

Iron deficiency anemia – inadequate intake of iron-containing foods, impaired iron absorption

Pernicious anemia – deficiency in vitamin B-12, usually due to lack or intrinsic factor necessary to absorb B-12 from the diet

Thalassemia – genetic in origin, RBC count is less than 2 million cells/cc, RBC’s are small and delicate due to hemoglobin molecule abnormality

Sickle-cell anemia – abnormal hemoglobin is spiky and sharp causing cells to become crescent shaped; cells rupture prematurely causing vessels to dam up and cause clots.

Polycythemia – excessive or abnormal increase in the number of erythrocytes. Viscosity is increased causing sluggish blood flow. Usual cause is bone cancer.

Secondary polycythemia – normal in those living at high altitudes due to secretion of erythropoietin in response to reduced O2 levels.

Leukocytes (WBC’s)Leukocytes (WBC’s)800: 1 RBC’s:WBC’s800: 1 RBC’s:WBC’s4,000-11,000 WBC/cc 4,000-11,000 WBC/cc (anymore = leukocytosis)(anymore = leukocytosis)

1% of total blood volume1% of total blood volumeContain nuclei and Contain nuclei and organellesorganelles

Protect from damage Protect from damage caused by viruses, caused by viruses, bacteria, toxins, parasites, bacteria, toxins, parasites, cancercancer

Display diapedesis (slip in Display diapedesis (slip in and out of blood vessels) and out of blood vessels) by amoeboid movementby amoeboid movementCan respond to chemical Can respond to chemical distress signals given out distress signals given out by damaged and dying by damaged and dying tissues (positive tissues (positive chemotaxis)chemotaxis)

2 major categories based 2 major categories based on structural and on structural and chemical characteristics:chemical characteristics:

Granulocytes – lobed nuclei and Granulocytes – lobed nuclei and stained granules – appears stained granules – appears “grainy”“grainy”Neutrophils Neutrophils

most numerous most numerous 2x RBC size 2x RBC size ½ of WBC population½ of WBC population3-5 lobes, hard to see 3-5 lobes, hard to see granulesgranules

digest bacteriadigest bacteria#’s elevate with staph, #’s elevate with staph, salmonella, systemic yeast, salmonella, systemic yeast, and appendicitis infectionsand appendicitis infections

BasophilsBasophilsLeast numerousLeast numerousSlightly larger than RBC’s,Slightly larger than RBC’s,U or S shaped nucleusU or S shaped nucleusFew purple granulesFew purple granulesWhen found in tissues are When found in tissues are called “mast cells”called “mast cells”

When bound to antibodies When bound to antibodies release heparin release heparin (anticoagulant) and (anticoagulant) and histamine (vasodilator) to histamine (vasodilator) to help WBC migrationhelp WBC migration

EosinophilsEosinophils2x RBC size2x RBC size1-4% of WBC population1-4% of WBC populationNucleus is bi-lobedNucleus is bi-lobedLarge, coarse red granulesLarge, coarse red granulesEat antigen-antibody Eat antigen-antibody complexescomplexes

Elevation can indicate Elevation can indicate allergic reactions, parasitic allergic reactions, parasitic worm or protozoan infectionsworm or protozoan infections

Reside in intestines, lungs Reside in intestines, lungs and skinand skin

Agranulocytes – lack granulesAgranulocytes – lack granulesLymphocytesLymphocytes

22ndnd most numerous most numerousFound in lymph tissueFound in lymph tissueSmall portion in bloodstreamSmall portion in bloodstreamImmune cell (T and B cells) Immune cell (T and B cells) productionproduction

Large, dark, purple nucleus Large, dark, purple nucleus which occupies most of the cellwhich occupies most of the cell

May have a thin rim of pale blue May have a thin rim of pale blue cytoplasmcytoplasm

Act against virus infected cells Act against virus infected cells and tumorsand tumors

MonocyteMonocyteLargest WBCLargest WBCAlso called “macrophages”Also called “macrophages”Gray-blue cytoplasm, Gray-blue cytoplasm, dark blue-purple U or dark blue-purple U or kidney shaped nucleuskidney shaped nucleus

Elevation may indicate a Elevation may indicate a chronic viral or bacterial chronic viral or bacterial infection such as leprosy or infection such as leprosy or tuberculosistuberculosis

1

2

3

4

5

BasophilBasophil

LymphocyteLymphocyte

MonocyteMonocyte

EosinophilEosinophil

NeutrophilNeutrophil

Production of WBC’sProduction of WBC’sLeukopoiesis – Leukopoiesis – hormonally triggeredhormonally triggered

All arise from All arise from hemocytoblastshemocytoblasts

Some mature in the Some mature in the thymus gland; others thymus gland; others in the bone marrowin the bone marrow

DisordersDisordersLeukemia – “white Leukemia – “white blood”blood”Abnormal WBC’s Abnormal WBC’s which fail to respond which fail to respond to regulatory to regulatory mechanismsmechanisms

Remain Remain unspecializedunspecialized

Enhanced ability Enhanced ability to divideto divide

Impair or Impair or suppress normal suppress normal bone marrow bone marrow functionfunction

Named according Named according to cell type: to cell type: “myelocytic” or “myelocytic” or “lymphocytic” “lymphocytic” leukemiasleukemias

lymphoblastic

promyelocytic

Infectious Infectious mononucleosismononucleosisViral (Epstein-Barr Viral (Epstein-Barr virus)virus)

Elevated monocytes Elevated monocytes and lymphocytesand lymphocytes

Leukopenia – decreased Leukopenia – decreased number of WBC’s; number of WBC’s; usually due to usually due to chemotherapy chemotherapy

Platelets Platelets (Thrombocytes)(Thrombocytes)Not true cells; are Not true cells; are fragmentsfragments

AnucleatedAnucleatedArise from stem cells, Arise from stem cells, become megakaryocyte become megakaryocyte then fragmentthen fragment

250,000 – 250,000 – 500,000 /cc500,000 /cc

Essential for Essential for clottingclotting

Degenerate in 10 Degenerate in 10 daysdays

Hemostasis – (stopping Hemostasis – (stopping blood flow)blood flow)Vasoconstriction – Vasoconstriction –

Constriction of blood Constriction of blood vessels triggered by vessels triggered by injury to smooth muscle injury to smooth muscle wall of vessel, wall of vessel, compression of vessel by compression of vessel by escaping blood, escaping blood, chemicals released by chemicals released by platelets, pain receptors platelets, pain receptors being stimulatedbeing stimulated

20-30 minutes of 20-30 minutes of reduced blood flowreduced blood flow

More efficient when More efficient when vessel is crushed vessel is crushed rather than blunt cut . rather than blunt cut . Blunt cuts have less Blunt cuts have less tissue damage and tissue damage and more profuse blood more profuse blood flowflow

Platelet PlugPlatelet Plug(+) charged platelet (+) charged platelet clings to the (-) charged clings to the (-) charged collagen tissue under collagen tissue under the endotheliumthe endothelium

Platelets develop Platelets develop swollen, spiky processesswollen, spiky processes

Platelet granules Platelet granules degenerate and release degenerate and release chemicalschemicals

This sets up a series This sets up a series of clotting events of clotting events which calls more which calls more platelets to the injury platelets to the injury sitesite

Aspirin inhibits plug Aspirin inhibits plug formationformation

Takes about 1 minuteTakes about 1 minute

Plug Formation

Coagulation (blood Coagulation (blood clotting)clotting)Prothrombin ------> Prothrombin ------> thrombinthrombin

Thrombin + fibrinogen Thrombin + fibrinogen = fibrin mesh= fibrin mesh

30 different factors 30 different factors involved; each require involved; each require CaCa++

Most are plasma Most are plasma proteins made in the proteins made in the liverliver

Absence of any one of Absence of any one of these factors results in these factors results in the inability to the inability to coagulate blood coagulate blood (hemophilia is an (hemophilia is an example)example)

Takes about 3-6 minutesTakes about 3-6 minutes

COAGULATION

Clot RetractionClot RetractionWithin 30 – 60 Within 30 – 60 minutes, platelets minutes, platelets shrink and pull shrink and pull fibrin fibers closer fibrin fibers closer together, further together, further sealing edges of sealing edges of woundwound

Fibrinolysis – Clot Fibrinolysis – Clot disposaldisposalWithin 2 days, plasmin Within 2 days, plasmin enzyme (activated by enzyme (activated by healing endothelium healing endothelium and factors in the clot and factors in the clot itself) will begin to eat itself) will begin to eat away at the clotaway at the clot

Fibrinolysis

PathologyPathologyThrombus – Thrombus – undesirable clot in an undesirable clot in an unbroken vesselunbroken vessel

Embolus – thrombus Embolus – thrombus that has broken free that has broken free and is traveling in the and is traveling in the circulatory systemcirculatory system

Any roughening of Any roughening of vessel walls can vessel walls can exacerbate this exacerbate this (atherosclerosis, (atherosclerosis, burns, burns, inflammation, inflammation, immobilization, etc)immobilization, etc)

Ruptured cholesterol plaque with thrombus

Thrombocytopenia – decrease in Thrombocytopenia – decrease in the number of platelets, causes the number of platelets, causes numerous, small, hemorrhages numerous, small, hemorrhages body wide (petechiae). Caused body wide (petechiae). Caused by anything that would destroy by anything that would destroy bone marrow (drugs, radiation). bone marrow (drugs, radiation). Diagnosed with a platelet count Diagnosed with a platelet count under 50,000/cc. Often need under 50,000/cc. Often need blood transfusionsblood transfusions

Impaired Liver Impaired Liver Function – can’t Function – can’t manufacture manufacture coagulants due to coagulants due to vitamin K deficiency, vitamin K deficiency, hepatitis, cirrhosis, hepatitis, cirrhosis, etcetc

HemophiliaHemophiliaType A – lack Type A – lack Factor VIII – Factor VIII – 83%83%

Type B – lack Type B – lack Factor IXFactor IX

Type C – lack Type C – lack Factor XFactor X

PlasmaPlasma90% water90% water10% “other stuff” – 10% “other stuff” – gases, hormones, gases, hormones, nutrients, wastes, ions, nutrients, wastes, ions, proteins (albumin, proteins (albumin, clotting proteins, clotting proteins, globulins), etc.globulins), etc.

TransfusionsTransfusionsLosses of 15 – 30 % causes Losses of 15 – 30 % causes paleness and weakness; more paleness and weakness; more than 30% = severe shockthan 30% = severe shock

RBC’s have specific antigens RBC’s have specific antigens (flags) on their surface(flags) on their surface

Plasma has Plasma has agglutinogens agglutinogens (soldiers) floating in it (soldiers) floating in it which attach to and which attach to and clump foreign antigensclump foreign antigens

Foreign blood will be Foreign blood will be agglutinated (clumped) agglutinated (clumped) and destroyedand destroyed

Type A – A antigens, Type A – A antigens, Anti-B agglutinogens – Anti-B agglutinogens – can receive A and O can receive A and O bloodblood

Type B – B antigens, Type B – B antigens, Anti-A agglutinogens – Anti-A agglutinogens – can receive B and O can receive B and O bloodblood

Type AB – A & B antigens, Type AB – A & B antigens, no agglutinogens – can no agglutinogens – can receive all blood types receive all blood types (universal recipient)(universal recipient)

Type O – no antigens, Anti-Type O – no antigens, Anti-A & Anti-B agglutinogens – A & Anti-B agglutinogens – can receive only O can receive only O (universal donor)(universal donor)

Rh factor is another type of antigenRh factor is another type of antigenTransfusion reactions can involve Transfusion reactions can involve lowered oxygen carrying ability, lowered oxygen carrying ability, blocked blood vessels, renal shut blocked blood vessels, renal shut down from liberated hemoglobin in down from liberated hemoglobin in the system, fever, chills, nausea, the system, fever, chills, nausea, vomitingvomiting

Any Questions?