Physiology, Lecture 4, Blood (slides)

BloodBlood Accounts for 8% of TBWAccounts for 8% of TBW 5L in females, 5.5L in males5L in females, 5.5L in males Cellular components:Cellular components: 1-1- RBCs RBCs : 99% of cells, hematocrit : 99% of cells, hematocrit

(packed cell volume) is 42% in (packed cell volume) is 42% in females & 45% in males.females & 45% in males.

2- 2- WBCs & plateletsWBCs & platelets : ~1% of total : ~1% of total blood volume blood volume

PlasmaPlasma 90% of plasma is water90% of plasma is water Serves as a medium for materials & also Serves as a medium for materials & also

absorbs and distributes much of the heat absorbs and distributes much of the heat from and to tissues.from and to tissues.

Organic & inorganic substances are Organic & inorganic substances are dissolved in plasmadissolved in plasma

Contents: ( % of plasma weight) :Contents: ( % of plasma weight) : 1- proteins 6-8%1- proteins 6-8% 2- waste, gases , hormones 1-3%2- waste, gases , hormones 1-3% 3- electrolytes (Na, Cl, K, Ca, HCO3- electrolytes (Na, Cl, K, Ca, HCO33) 1%) 1%

Fig. 11-1, p. 316

Packed cellvolume, orhematocrit

Plasma = 55% of whole blood

“Buffy coat”<1%

Platelets

White blood cells

Red blood cells =45% of whole blood

Functions of Plasma proteins:Functions of Plasma proteins: 1- establish an osmotic gradient (colloid)1- establish an osmotic gradient (colloid) 2- pH buffering2- pH buffering 3- bind cholesterol, iron, and thyroid 3- bind cholesterol, iron, and thyroid

hormonehormone 4- blood clotting factors4- blood clotting factors 5- inactivate precursor molecules 5- inactivate precursor molecules (angiotensenogen for example)(angiotensenogen for example) 6- 6- αα-globulins, immunoglobulins, antibodies-globulins, immunoglobulins, antibodies

ErythrocytesErythrocytes 5 million/ 5 million/ μμL or cubic mm L or cubic mm Main function: oxygen transporterMain function: oxygen transporter Flat, disc-shaped, indented in the middle Flat, disc-shaped, indented in the middle

(doughnut), biconcave discs(doughnut), biconcave discs Shape benefits:Shape benefits: 1- Biconcave disc provides large surface1- Biconcave disc provides large surface 2- thin membrane provides easy transport2- thin membrane provides easy transport Hemoglobin: consists of globin protein (4 Hemoglobin: consists of globin protein (4

polypeptide chains), and 4 iron containing non-polypeptide chains), and 4 iron containing non-protein groups (heme)protein groups (heme)

Each iron in heme can pick up one molecule of OEach iron in heme can pick up one molecule of O22 reversiblyreversibly

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Fig. 11-3, p. 317

Polypeptide chain

Polypeptide chainPolypeptide chain

Polypeptide chain

Heme groups

OO22 is poorly soluble in plasma so 98.5% of O is poorly soluble in plasma so 98.5% of O22 is is boundbound

Hb is reddish when bound, & bluish when notHb is reddish when bound, & bluish when not Hb can carry: 1- COHb can carry: 1- CO22 2- acidic hydrogen ion portion of 2- acidic hydrogen ion portion of carbonic acidcarbonic acid 3- CO3- CO 4- nitric-oxide (NO) : vasodilator4- nitric-oxide (NO) : vasodilator 250 million Hb molecules in RBC can carry 1 250 million Hb molecules in RBC can carry 1

billion Obillion O22 molecules molecules

25-30 trillion RBCs live in the blood 25-30 trillion RBCs live in the blood for a short time and they must be for a short time and they must be replaced at the rate of 2-3million/secreplaced at the rate of 2-3million/sec

No DNA or RNA No DNA or RNA no protein no protein synthesis for repair, growth, or synthesis for repair, growth, or divisiondivision

Life span is 120 days Life span is 120 days membrane membrane becomes fragile and rupturesbecomes fragile and ruptures

Most old RBCs die in the spleen Most old RBCs die in the spleen

ErythropoiesisErythropoiesis The erythrocyte factory is the bone marrowThe erythrocyte factory is the bone marrow In children the bone marrow is red, while in adults In children the bone marrow is red, while in adults

the marrow is yellow except for the sternum, ribs, the marrow is yellow except for the sternum, ribs, & the upper ends of long limb bones in which the & the upper ends of long limb bones in which the bone marrow is redbone marrow is red

Stem cells in bone marrow: 0.1% of total cells Stem cells in bone marrow: 0.1% of total cells (pluripotent stem cells)(pluripotent stem cells)

Erythropoietin controls erythropoiesis:Erythropoietin controls erythropoiesis: Decreased O2 concentrationDecreased O2 concentration kidney kidney

stimulationstimulation erythropoietin secretion erythropoietin secretion bone bone marrow stimulationmarrow stimulation increased RBCs increased RBCs increased increased O2 concentrationO2 concentration erythropoietin secretion is erythropoietin secretion is turned off turned off

PlateletsPlatelets 250 million/mL 150-350thousand/mm250 million/mL 150-350thousand/mm Cell fragments shed from Cell fragments shed from

megakaryocytes (large B.M cells)megakaryocytes (large B.M cells) Mother stem cell gives RBCs, WBCs, & Mother stem cell gives RBCs, WBCs, &

megakaryocytes which produces 100 megakaryocytes which produces 100 platelets (vesicles)platelets (vesicles)

Life span is 10 days, then removed by Life span is 10 days, then removed by macrophagesmacrophages

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hemostasishemostasis Stopping hemorrhage from small Stopping hemorrhage from small

damaged capillaries, arterioles, and damaged capillaries, arterioles, and venulesvenules

Bleeding from a vein or an artery Bleeding from a vein or an artery cannot be stopped by hemostasis but cannot be stopped by hemostasis but by a different mechanism:by a different mechanism:

1-vasospasm1-vasospasm 2-platelet plug formation2-platelet plug formation 3-blood coagulation (clotting)3-blood coagulation (clotting)

Vascular spasmVascular spasm Constriction of vessel because of Constriction of vessel because of

intrinsic responseintrinsic response Triggered by a paracrine released Triggered by a paracrine released

from injured endotheliumfrom injured endothelium Leads to slow blood flow and Leads to slow blood flow and

endothelial surfaces adherence endothelial surfaces adherence because they become stickybecause they become sticky

Platelet aggregationPlatelet aggregation Vessel injuryVessel injury exposed collagen exposed collagen

platelets activationplatelets activation platelet plug platelet plug formationformation the plug releases adenosine the plug releases adenosine diphosphate(ADP)diphosphate(ADP) surrounding surface surrounding surface becomes stickybecomes sticky more platelets adhere more platelets adhere another pluganother plug more ADP more ADP (POSITIVE (POSITIVE FEEDBACK)FEEDBACK)

Increased ADP & other chemicalsIncreased ADP & other chemicals stimulates the release of NO & stimulates the release of NO & prostacyclin from adjacent endotheliumprostacyclin from adjacent endothelium aggregation inhibition aggregation inhibition

Aggregated platelet plugAggregated platelet plug Functions:Functions: 1- contracts actin-myosin complex in 1- contracts actin-myosin complex in

aggregate to strengthen the plugaggregate to strengthen the plug 2-releases vasoconstrictors2-releases vasoconstrictors 3-relases chemicals which enhance 3-relases chemicals which enhance

blood coagulationblood coagulation The aggregated plug is enough to The aggregated plug is enough to

stop small tears in capillariesstop small tears in capillaries

Fig. 11-7, p. 322

Platelet

Vessellumen

Vesselwall

Adenosinediphosphate(ADP)

Prostacyclinand nitric acid

Normal endothelium

Inhibits plateletaggregation

Normal endothelium

Prostacyclinand nitric acid

CollagenAggregatingplatelet plug Exposed collagen

at site ofvessel injury

Clot formationClot formation The ultimate step in clot formation is the The ultimate step in clot formation is the

conversion of fibrinogen (large soluble plasma conversion of fibrinogen (large soluble plasma protein) to fibrin ( insoluble threadlike molecules)protein) to fibrin ( insoluble threadlike molecules)

This reaction is catalyzed by thrombin then fibrin This reaction is catalyzed by thrombin then fibrin forms netlike meshwork that traps blood cells and forms netlike meshwork that traps blood cells and plugs.plugs.

Thrombin is in plasma as prothrombin which can Thrombin is in plasma as prothrombin which can be activated by the clotting cascadebe activated by the clotting cascade

Clotting cascade: 12 plasma clotting factors, once Clotting cascade: 12 plasma clotting factors, once the 1the 1stst factor is activated it will activate th next factor is activated it will activate th next factor and so on.. factor and so on..

several steps need Ca & platelet factor 3 (PF3) several steps need Ca & platelet factor 3 (PF3)

secreted by the plug secreted by the plug

Clotting cascadeClotting cascade Intrinsic pathway: clotting within damaged blood Intrinsic pathway: clotting within damaged blood

vessel or of a blood sample in a test tubevessel or of a blood sample in a test tube Extrinsic pathway: a shortcut that only requires 4 Extrinsic pathway: a shortcut that only requires 4

steps:steps: contact with tissue factors external to the bloodcontact with tissue factors external to the blood

trauma of tissuetrauma of tissue which releases a protein which releases a protein complex (thromboplastin)complex (thromboplastin) which activates which activates factor X that clots the blood that escaped into the factor X that clots the blood that escaped into the tissue before the vessel was sealed offtissue before the vessel was sealed off

Both mechanisms operate simultaneously and Both mechanisms operate simultaneously and

takes around 3-6 minutes takes around 3-6 minutes

Fig. 11-9, p. 324

Clot retractionClot retraction Platelets in plug or clot contract and Platelets in plug or clot contract and

shrinks the fibrin meshwork pushing the shrinks the fibrin meshwork pushing the edges of the damaged vessel closer and edges of the damaged vessel closer and this retraction squeezes the seumthis retraction squeezes the seum

Vessel repair:Vessel repair: aggregated platelets aggregated platelets release chemicals which help promoting release chemicals which help promoting the invasion of fibroblasts (fiber formers) the invasion of fibroblasts (fiber formers) from connective tissues and a scar is from connective tissues and a scar is formed formed

Clot dissolutionClot dissolution Plasmin (fibrinolytic enzyme) is present in plasma Plasmin (fibrinolytic enzyme) is present in plasma

as plasminogen which is activated by factors like as plasminogen which is activated by factors like tissue plasminogen activator (tPA) from tissues tissue plasminogen activator (tPA) from tissues (lungs) or factor XII, after its activation it breaks (lungs) or factor XII, after its activation it breaks down the fibrin meshworkdown the fibrin meshwork

Phagocytic cells remove the dissolved productsPhagocytic cells remove the dissolved products

Continuous clotting in vessels by activated fibrin Continuous clotting in vessels by activated fibrin can be handled by plasmincan be handled by plasmin

ThromboembolismThromboembolism Thrombus: an attached clot Thrombus: an attached clot Embolism: a freely floating clot Embolism: a freely floating clot Causes:Causes: 1-rough surface atherosclerosis1-rough surface atherosclerosis 2-imbalance between clotting & anti-clotting2-imbalance between clotting & anti-clotting 3-slow blood flow3-slow blood flow 4-widespread clotting triggered by the release of 4-widespread clotting triggered by the release of tissue thromboplastin because of trauma tissue thromboplastin because of trauma

LeukocytesLeukocytes Mobile units of the immune defense systemMobile units of the immune defense system The immune system: leukocytes and their The immune system: leukocytes and their

derivatives, and also a variety of plasma proteinsderivatives, and also a variety of plasma proteins Defeng against invading pathogens (bacteria, Defeng against invading pathogens (bacteria,

viruses)viruses) Clean RBCs and tissue debrisClean RBCs and tissue debris Identifies and destroys abnormal or mutant cells Identifies and destroys abnormal or mutant cells

(immune surveillance) –internal defense (immune surveillance) –internal defense mechanism against cancer-mechanism against cancer-

WBCs function by “seek & attack” strategy WBCs function by “seek & attack” strategy Bacteria and viruses are major targets Bacteria and viruses are major targets

Types of leukocytes vary in structure Types of leukocytes vary in structure and function:and function:

1-polymorphonuclear granulocytes1-polymorphonuclear granulocytes: : the nucleus is segmented, and the the nucleus is segmented, and the cytoplasm contains granules (red in cytoplasm contains granules (red in eosinophils, blue in basophils):eosinophils, blue in basophils):

a-neutrophils b-eosinophils c-a-neutrophils b-eosinophils c-basophilsbasophils

2-mononuclear agranulocytes: 2-mononuclear agranulocytes: a-monocytes b-lymphocytesa-monocytes b-lymphocytes

All leukocytes are from undifferentiated All leukocytes are from undifferentiated pluripotent stem cells in the red B.M which pluripotent stem cells in the red B.M which differentiate into various committed cell differentiate into various committed cell lineslines

Granulocytes and monocytes are only Granulocytes and monocytes are only produced in the bone marrowproduced in the bone marrow

Lymphocytes originally are derived from Lymphocytes originally are derived from precursor cells in the bone marrow while precursor cells in the bone marrow while most new lymphocytes are produced in most new lymphocytes are produced in the lymphoid tissues (lymph nodes) onlythe lymphoid tissues (lymph nodes) only

Different hormones direct the Different hormones direct the differentiation and proliferation of WBCs differentiation and proliferation of WBCs such as the granulocyte-colony stimulating such as the granulocyte-colony stimulating factorfactor

WBC count averages 7000/mm and 2/3 of WBC count averages 7000/mm and 2/3 of which are granulocyteswhich are granulocytes

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Leukocytes functionsLeukocytes functions 1- Neutrophils:1- Neutrophils: a- as a phagocytic scavenger to clean up debrisa- as a phagocytic scavenger to clean up debris b- release neutrophil extracellular traps(NETs) b- release neutrophil extracellular traps(NETs) containing bacteria killing chemicalscontaining bacteria killing chemicals c- they increase in acute bacterial infectionc- they increase in acute bacterial infection 2- Eosinophils:2- Eosinophils: a- they increase in allergic reactions (asthma, a- they increase in allergic reactions (asthma,

hay fever) and also in parasitic infections (worms)hay fever) and also in parasitic infections (worms) b- secrete substances that kill worms (parasites)b- secrete substances that kill worms (parasites)

3- Basophils:3- Basophils: a- synthesize histamine & heparina- synthesize histamine & heparin b- life span : 1 day in blood & 3-4 days in tissuesb- life span : 1 day in blood & 3-4 days in tissues

4- Monocytes:4- Monocytes: a- professional phagocytesa- professional phagocytes b- released from B.M to blood for 1-2 days then to b- released from B.M to blood for 1-2 days then to

the tissue they become large and mature the tissue they become large and mature macrophages that lives for months or yearsmacrophages that lives for months or years

5- Lymphocytes:5- Lymphocytes: a- provide immune defense against a- provide immune defense against

targets for which they are specifically targets for which they are specifically programmedprogrammed

b- b- B-cellsB-cells produce antibodies to bind and produce antibodies to bind and kill invaderskill invaders

c- c- T-cellsT-cells directly destroy invaders by directly destroy invaders by releasing chemicals through punching releasing chemicals through punching holes in targeted cells (body cells invaded holes in targeted cells (body cells invaded by viruses or cancer)by viruses or cancer)

d- life span is 100-300 days but they d- life span is 100-300 days but they spend only few hours in the blood spend only few hours in the blood