sistem darah 1 (blood circulation)

8/2/2019 Sistem Darah 1 (Blood Circulation)

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The Blood


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The blood contains a solid part and a liquid part.The solid part consists of the blood cellsand the liquid part is the plasma.

If one takes a sample of blood, treats it with an agent to prevent clotting,and spins it in a centrifuge,

nthe red cells settle to the bottomnthe white cells settle on top of them forming the "buffy coat".

The fraction occupied by the red cells is called the hematocrit.Normally it is approximately 45%. Values much lower than this are a signof anemia.

Thus hematocrit is the percentage of red blood cells in the blood.


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General Components of Bloodn Whole Blood can be broken into 2 main components:

n Plasma (46-63%)

n Formed elements (37-54%). Plasma itself consists primarily of:

n Water (92%)n Plasma Proteins (7%)n Other solutes (1%).

n The formed elements consist of:n Red blood cells (99.9%)n White blood cells (>0.1%)n Platelets (>0.1%).


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Functions of the BloodBlood performs two major functions:

n transport through the body ofn oxygen and carbon dioxide

n food molecules (glucose, lipids, amino acids)

n ions (e.g., Na+, Ca2+, HCO3)n wastes (e.g., urea)

n hormones

n heat

n defense of the body against infections and otherforeign materials. All the WBCs participate inthese defenses.


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Other functions of blood. They include:

n Transport of dissolved gases, nutrients, hormones, andmetabolic wastes.

n Regulation of the pH and electrolyte composition ofinterstitial fluids throughout the body.

n Restriction of fluid losses (in event of injury).n Defense against toxins and pathogens.


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Composit ion of PlasmaPlasma is the straw-colored liquid in which the blood cells aresuspended. It is the liquid portion of the blood

Component PercentWater ~92

Proteins 68

Salts 0.8

Lipids 0.6

Glucose (blood sugar) 0.1


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Serum Proteins ( in the Plasma )n

Proteins make up 68% of the blood. They are aboutequally divided between serum albumin and a greatvariety ofserum globulins.

n After blood is withdrawn from a vein and allowed to

clot, the clot slowly shrinks. As it does so, a clear fluidcalled serum is squeezed out. Thus:

n Serum is blood plasma without fibrinogen and otherclotting factors.


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Formation of different types of blood cells from stem cells.


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A Red Blood Cell

n Red blood cell synthesis is known as erythropoiesis. In the adult, allblood cell formation (i.e., synthesis of RBCs, WBCs, and platelets)occurs in the red bone marrow.


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RED BLOOD CELL FORMATION ( Erythropoiesis )n In health, erythropoiesis is regulated so that the number of

circulating erythrocytes is maintained within a narrow range.Normally, a little less than l% of the body's total red blood cells areproduced per day and these replace an equivalent number that havereached the end of their life span. However that still represents ahuge 200,000,000,000 cells

n Erythropoiesis is stimulated by hypoxia (lack of oxygen). However,oxygen lack does not act directly on the haemopoietic tissues butinstead stimulates the production of a hormone, e ry th ropo i e t i n .This hormone then stimulates haemopoietic tissues to produce redcells.

n Erythropoietin is a glycoprotein. It is inactivated by the liver andexcreted in the urine. It is now established that erythropoietin isformed within the kidney by the action of a renal erythropoieticfactor e r y t h r o gen i n .

n Erythrogenin is present in the juxtaglomerular cells of the kidneysand is released into the blood in response to hypoxia in the renalarterial blood supply.

n Various other factors can affect the rate of erythropoiesis byinfluencin er thro oietin roduction.


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What happens to the iron?Iron will be stored in the liver as well astransported to red bone marrow (to beincorporated in new RBCs) and other tissues

Iron is transported in the blood as a proteincomplex called transferrin and stored withinliver cells.


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Hematocritn An essential test used to examine blood is the hematocrit. The hematocrit is a

measure of the percentage of whole blood occupied by RBCs.

n Average value in a male is 47% (range of 42-52%).

n Average in a female is 42% (range of 37-47%).

n HCT can be determined by centrifuging a sample of blood so that all the

formed elements come out of suspension - we will do this in lab!n Since leukocytes and platelets make up far less than 1% of the blood, it can

be assumed that: (100-HCT) = % of blood occupied by plasma.


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Types of WBCs:

n They can be classified as to whether or not they containgranules that take up Wright's stain and are visible withthe light microscope.

n Granulocytesn Contain visible stained granules. Includes:

n Basophilsn Eosinophilsn Neutrophils.n Agranulocytes

n

Do not contain stained visible granules. Includes:n Lymphocytesn Monocytes.


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- 50-70% of circulating WBCs.- Cytoplasm is packed with pale "neutral" colored granules that contain bactericidalcompounds.- Mature neutrophils have a segmented nucleus - and are thus known aspolymorphonuclear leukocytes.- About 12 um in diameter.

- Highly mobile and generally the first WBCs to arrive at a site of injury.- Specialize in attacking and digesting bacteria that have been "marked" fordestruction.- Lifespan of about 6 hrs to a few days.

Neutrophils


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n 2- 4% of circulating WBCs.n Similar in size to neutrophils but have reddish-orange staining

granules.n Functions:

n Phagocytize antibody-coated bacteria, protozoa, and cellular debris.n Exocytose toxic compounds onto the surface of pathogens, particularly

large multicellular parasites such as flukes or parasitic worms.n They increase in # dramatically during a parasitic infection.n Also sensitive to allergens and increase in # during allergic reactions

as well.n Typical lifespan of 8 - 12 days.

Eosinophils


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Basophils

n Less than 1% of circulating leukocytes.n Smaller than eosinophils and neutrophils.n Contain granules that appear deep purple or blue.n Migrate to injury sites and discharge the contents of their granules:n Histamine

n Vasodilator and increaser of capillary permeability.

n Heparinn An anticoagulant.

n These 2 chemicals enhance the local inflammation initiated by mast cells andattract other WBCs.


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Monocytes

n 2- 8 % of circulating WBCs.n Almost 2 x as big as an RBC.

n Nucleus is large & tends to be oval or kidney-shaped.n Individual monocytes use the bloodstream as a highway,

staying in the circulation for only about 24hrs before anentering peripheral tissues to become a tissuemacrophage, an aggressive phagocyte.

n Lifespan can be up to several months.


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Lymphocytes

n 20 30 % of circulating WBCs.n Slightly larger than RBCs.n In blood smears, you typically only see a thin halo of cytoplasm around a relatively large

nucleus.n Continuously migrate from the bloodstream into the peripheral tissues and back into the

bloodstream.n Circulating lymphocytes are only a minute fraction of the total # in the body. Most are in

other connective tissues and in lymphatic organs.n Circulating blood contains 2 main classes of lymphocytes:

n T Lymphocytes: Defend against foreign cells and tissues and coordinate the immune response.

n B Lymphocytes: Produce and distribute antibodies - proteins that attack foreign molecules.n Lifespan 2 to 3 days or about 200 days.


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n Normal values of RBC and WBC


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Hemoglobin (Hgb)Men:1418 grams per deciliter (g/dL) or 8.711.2 mmol/L (SI units)Women:1216 g/dL or 7.49.9 mmol/L

Red blood cell (RBC) count

Men: 4.66.2 million RBCs per microliter (L) or 4.66.2 x 1012/Liter (SIunits)Women: 4.25.4 million RBCs per L or 4.25.4 x 1012/L

Children: 4.64.8 million RBCs per L or 4.64.8 x 1012/L

Hematocrit (HCT)Men: 40%54%Women: 37%47%


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Red blood cell indicesMean corpuscular volume (MCV):

80100 femtoliters (fL)

Mean corpuscular hemoglobin (MCH): 2832 picograms (pg)

Mean corpuscular hemoglobin concentration(MCHC): 3236 grams per deciliter (g/dL)


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n WBC count: 4,50011,000/L

n polymorphonuclear neutrophils: 18007800/L; (5070%)

n band neutrophils: 0700/L; (010%)

n lymphocytes: 10004800/L; (1545%)

n monocytes: 0800/L; (010%)

n

eosinophils: 0450/L; (06%)n basophils: 0200/L; (02%)


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Platelet (thrombocyte) count

140,000450,000 platelets permm3 or 150400 x 109/Liter (SI

units)


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Plateletsn Platelets are cell fragments produced frommegakaryocytes . Blood normally contains 150,000

350,000 per microliter (l) or cubic millimeter (mm3).

This number is normally maintained by a homeostatic(negative-feedback) mechanism .n If this value should drop much below 50,000/l, there is a

danger of uncontrolled bleeding because of the essentialrole that platelets have in blood clotting.

n Platelets contains chemical substances or blood factorswhich play a major role in blood clotting.


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n The production ofplateletsis called thrombopoiesisn Flattened, disk-like cell fragments that are about 1um by 4um.n Act as a participant in the vascular clotting system.n Sometimes referred to as thrombocytes.n Continuously being replaced. Each platelet circulates for 9-12 days

before being removed by splenic macrophages.n On average there are 350,000 platelets per uL of blood.n Produced in the bone marrow. Large cells called megakaryocytes

release fragments (platelets) into the circulation


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Formation of Platelets


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This looping diagrammatic animation shows the process of plateletformation from a megakaryocyte


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What do platelets do?

n Transport of chemicals integral to the

clotting process.n By releasing enzymes and other factors,

platelets help initiate the clotting process.

n Formation of a temporary patch (called aplatelet plug) in the wall of a damagedblood vessel.


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Blood clotting

n Vascular Phasen Damage to the wall of a blood vessel will obviously affect those cells that

comprise the wall.n The endothelial cells (simple squamous epithelium that lines the blood vessel

lumen) at the site of an injury will:n Have their basement membrane exposed.n Release a variety of chemicals.n Become "sticky."

n The smooth muscle cells in the blood vessel wall also respond to damage. They

CONTRACT. By contracting, the blood vessel diameter decreases which helps toreduce blood loss and reduce the pressure on the damaged area.


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n Platelet Phasen

Platelets begin to attach to the sticky endothelial cells, the basement membrane, and toexposed collagen fibers.n As platelets "stick," they are activated and they release chemicals that:

n Attract and activate more platelets.n Cause local vasoconstriction (contraction of blood vessel smooth muscle and a subsequent

decrease in the diameter of the blood vessel lumen).

n Eventually, we are left with a mass of platelets that temporarily plugs the leak in the

damaged blood vessel wall.n It should be noted that intact endothelial cells release a chemical called prostacyclin which


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n Coagulation Phasen Now we need to create a more permanent seal that can effectively cover the break while

repairs take place. In other words, we need a clot.n The coagulation phase is a sequence of chemical reactions that culminate in the

conversion of fibrinogen (a soluble circulating plasma protein made by the liver) into ameshwork of the insoluble protein fibrin.

n The fibrin meshwork will grow and cover the surface of the platelet plug. RBCs andadditional platelets are trapped in this tangle forming a blood clot that will effectively sealthe walls of the damaged blood vessel.

n Coagulation requires calcium as well as clotting factors - several different proteins

primarily synthesized by the liver.n Many clotting factors are proenzymes (inactive enzymes) that have to be converted to active

enzymes before they can direct essential reactions in the clotting process.

n The synthesis of some of the clotting factors requires vitamin K.

n During the coagulation phase enzymes and proenzymes interact. The activation of oneproenzyme creates an active enzyme that activates another proenzyme that will thenactivate a third and so on yielding a chain reaction or cascade. You can think of it kind oflike a row of dominos falling down.


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n There are actually 2 main cascades involved in the clottingprocess: the extrinsic pathway,and intrinsic pathway.

n Extrinsic Pathwayn Begins with the release of tissue factor by damaged endothelial cells or

peripheral tissues.n The greater the damage, the more tissue factor released, and the faster

clotting will occur.n In a few short steps, a chemical called prothrombin activator will have

been formed. Because only a few steps are required, the extrinsic pathforms prothrombin activator rather quickly.

n Intrinsic Pathwayn

Begins with the exposure of collagen which starts the activation cascadeof several proenzymes eventually resulting in the production ofprothrombin activator.

n Because there are several steps, the intrinsic path does not makeprothrombin activator as fast as the extrinsic path. However, multiplesteps allows for more amplification which means more prothrombinactivator will be made.


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Blood clot ( electron microscopy )


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n How do we get rid of the clot?n

Fibrinolysisn As repairs proceeds, the clot gradually dissolves. This

dissolution is known as fibrinolysis.n Fibrinolysis begins with the activation of the proenzyme

plasminogen by 2 enzymes:n Thrombin activated in the common pathway.n Tissue plasminogen activator released by damaged tissue.

n Once plasminogen is turned into plasmin, the plasmindigests the fibrin strands and erodes the foundation of the

clot.______________________________________________

Plasmin

BLOOD CLOT ---------------------------- clot dissolved


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The End

sistem darah 1 (blood circulation)

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