206 blood.ppt revised ps

8/12/2019 206 Blood.ppt Revised Ps

http://slidepdf.com/reader/full/206-bloodppt-revised-ps 1/46

Blood – Physical

Characteristics

• Adult ♂ contains 5-6L

• Adult ♀ contains 4-5L

• T is about 100.4 F

– Is this higher or lower than normal body T ?• 5 times as viscous as water

– Is it more or less resistant to flow than water?

– What accounts for its viscosity?

• pH ranges from 7.35 – 7.45 (slightly alkaline)

• Color ranges from scarlet (oxygenated blood) toa deep red (deoxygenated blood).



Whole Blood

Plasma

(46-63%)

Formed Elements

(37-54%)

1. Water (92%)

2. Plasma Proteins (7%)

3. Other Solutes (1%)

1. Red Blood Cells (99.9%)

2. Platelets

3. White Blood Cells

(0.1%)



Functions of Blood

• Transportation ofdissolved gases,nutrients, hormones, andmetabolic wastes

• Regulation of the pH andelectrolyte composition ofinterstitial fluidsthroughout the body

• Restriction of fluid losses

• Defense against toxinsand pathogens

• Stabilization of bodytemperature

These red blood cells function

in oxygen transport



Blood and

Transportation• Red blood cells are packed

with the protein hemoglobin (Hb) which carries O2

• CO2 is carried by Hb, anddissolved in plasma inmultiple ways

• Nutrients absorbed at the GI tract, or released by the liveror adipocytes, are distributed by blood

• Hormones (blood-borne chemical messengers) are

transported from the endocrine glands where they’reproduced to their target organs via the bloodstream

• Metabolic wastes produced by tissue cells are absorbedby the blood and carried to the kidneys for excretion



Blood & Regulation

• Blood absorbs heat from activeskeletal muscles and distributesit to other tissues. If body T isalready high, that heat will belost across the skin surface. Ifbody T is too low, that heat willbe directed to the brain and toother T sensitive organs.

• The blood absorbs andneutralizes the acids generatedby active tissues (e.g., lacticacid from skeletal muscles).

• The blood acts as both a conduitand reservoir for importantelectrolytes (Na+, Ca2+, etc.)

• Blood volume is regulated inresponse to the body’s waterlevels.

The above represents a relative

distribution of blood in response

to warm and cold ambient

temperatures.



Blood & Protection

• Blood transports whiteblood cells, specializedcells that migrate intoperipheral tissues to fightinfections and remove

debris.• Blood delivers antibodies,

proteins that attackinvading organisms andforeign compounds.

• Blood contains enzymesthat respond to a break ina blood vessel wall byforming a clot to restrict

further fluid loss.

Above, we have a SEM image of

a blood clot. Notice the RBCs.



Red Blood Cells

(Erythrocytes)

• Most abundant bloodcells (99.9% of formedelements) – In ♂, 1µL of blood contains

4.5-6.3 million RBCs

– In ♀, 1µL of blood contains4.2-5.5 million RBCs

• Contains the red pigmenthemoglobin which bindsand transports O2 and

CO2

• Each RBC is a biconcave disc

Diameter → 8µm

Thickness → 2.5µm



Erythrocytes

• Why a biconcave disc? – Provides a large surface area

for O2 entry/exit

– Enables them to bend and

flex when entering small

capillaries

• RBCs lack a nucleus and

most organelles.

– Instead they are simply

membranous bags ofhemoglobin

– What is a functional

advantage of the fact that the

RBC lacks mitochondria?

Here, we have an RBC bending tofit thru a small capillary



Hemoglobin

• Large protein consistingof 4 polypeptides – 2 chains and 2 β chains

• Each chain contains a

single molecule ofheme, an iron-containing

pigment – The iron ion in heme is able to

reversibly bind an oxygen molecule.

– Meaning, O2 can bind to Hb at thelungs and then be released at the

tissues

• Based on the above, how

many molecules of O2 can

each Hb protein bind?

Note the 2 chains and 2

β chains. Notice howeach has an associated

heme molecule with an

iron atom.



RBC Formation (Erythropoiesis)

• In the adult, all blood cell formation (including erythropoiesis)

occurs in the red bone marrow

• All blood cells develop from stem cells called hemocytoblasts

Hemocytoblast

Myeloid Stem Cell

Lymphoid Stem Cell

Red Blood CellsMonocytes

Platelets

Granulocytes

Lymphocytes



Control of Erythrocyte

Production

Figure 10.5



Lifecycle of an

RBC• RBCs are subjected to

incredible mechanicalstress. – Why are they unable to

synthesize replacements for

damaged parts?• After ≈120d, the RBC cell

membrane ruptures, or thedamage is detected byphagocytic cells and the

RBC is engulfed.• If the RBC hemolyzes, itscontained Hb will beexcreted by the kidneys

Above, we have a macrophage

phagocytizing multiple RBCs



• Once an RBC has been engulfed & broken down by a phagocyticcell, each component of Hb has a different fate.

1. Globular proteins• Disassembled into component amino acids and

metabolized by the cell or released into the circulation foruse by other cells

2. Heme• Stripped of its iron and converted to bilirubin, which has

an orange-yellow color.

• Bilirubin is released into the circulation where it binds to

albumin and is transported to the liver.• Liver modifies and then secretes bilirubin into

the small intestine as a component of bile. – If the bile ducts are blocked, or if the liver is unable

to absorb/excrete bilirubin, plasma [bilirubin] risesand diffuses into peripheral tissues where it can

impart a yellow color to the skin and sclera of theeye ( jaundice)

• Inside the large intestine, bacteria convert the bilirubin intourobilinogens and stercobilinogens.

• Some urobilinogens are absorbed back into the circulationand excreted by the kidneys as urine. Urobilinogen givesurine its yellow color. The brownish color of feces is dueto the presence of urobilinogens and stercobilinogens.



Complete Blood Count (CBC)

• Determination of the number of red and white blood cellsper mL of blood

• One of the most routinely performed clinical tests and avery valuable screening and diagnostic technique

• Can be performedmanually or via anelectric counter

• Different disorderscan have a dramatic

effect on the totalnumber or relativeproportion of bloodcells.



Hematocrit

• Percentage of whole blood occupied bypacked red blood cells

• Average in a ♂ is 46 (range of 40-54)

• Average in a ♀ is 42 (range of 37-47)

– Greater in ♂ b/c androgens (e.g.,testosterone) stimulate RBC synthesiswhile estrogens do not

• Determined by centrifuging a bloodsample so that all formed elements

come out of suspension• Low Hct values may indicate anemia

whereas high values may indicatepolycythemia



Polycythemia

• An elevated hematocrit with anormal blood volume

• I.e., an increase in thenumber of erythrocytes in theblood.

• May be primary (polycythemia vera) and due to cancer of the

bone marrow

• May be secondary when lessoxygen is available orerythropoietin (kidneyhormone that stimulates

RBC synthesis) production increases.• How does polycythemia affect blood viscosity and thus affect bloodflow?

• Polycythemia can be treated by blood dilution – removing bloodand replacing it with isotonic saline.

• Endurance athletes often attempt to induce polycythemia as ameans of increasing their athletic performance. Why?



Anemia

• Condition where the blood has an abnormally lowoxygen-carrying capacity

• Symptom rather than a disease in/of itself

• Why are anemic individuals oftenshort of breath, fatigued, and chilly?

• Types: – Hemorrhagic – Hemolytic

– Aplastic – Iron-deficiency

– Pernicious – Sickle Cell

– Thalassemia



Anemia

• Hemorrhagic – Results from blood

loss (i.e., RBC loss)

– Can be acute (stabwound perhaps) orchronic (due tohemorrhoids or anundiagnosed bleedingulcer)

• Hemolytic – RBCs rupture (lyse) prematurely

– Can be due to hemoglobin abnormalities, mismatched bloodtransfusions, parasitic or bacterial infection, or autoimmune.

• Aplastic – Results from destruction of red bone marrow from bacterial toxins,

drugs, or radiation. Not only impacts RBCs but WBCs and plateletsas well. Why ?

Compare the 2 slides of red bone marrow.

Blue dots indicates developing blood cells.

Left-hand slide is during aplastic anemia;

right-hand slide is almost back to normal



Anemia

• Iron-Deficiency

– What role does iron play in oxygen transport? – Iron-deficiency anemia can be secondary to

hemorrhagic anemia or can occur due toinadequate iron intake or absorption

• Pernicious

– Due to a lack of Vitamin B12 intake or absorption. – Stomach mucosa produces a substance calledintrinsic factor which is necessary for Vitamin B12 absorption.

– Lack of intrinsic factor is often a cause ofpernicious anemia

• Thalassemias – Often seen in people of

Mediterranean origin.

– One of the globin genes isabsent or faulty.



Sickle-cell Anemia

• A single mutation in the genefor the β chain of the globinmolecule results in abnormalhemoglobin (HbS)

• Due to the structural change,the β chains link togetherand become stiff rods underlow-O2 conditions.

• This causes the RBCs to

become sickle-shaped andthese malformed RBCs canthen block and clog smallblood vessels.



Erythroblastosis Fetalis

• A type of hemolytic anemia

• Suppose we have an Rh- mom whose 1st child is Rh+. At birth, the placenta ruptures and the baby’s bloodmixes with the mother’s blood. This sensitizes the momto the Rh antigen and she begins to produce antibodiesagainst the Rh antigen.

• The 1st child is fine – he/she has already been born.

• However if the mom has a 2nd Rh+ child, her anti-Rhantibodies will cross the placenta and begin to attack thefetal RBCs.. This condition is erythroblastosis fetalis(a.k.a. hemolytic disease of the newborn)

• The baby becomes anemic and hypoxic; brain damageand death may result if blood transfusions are notperformed.



http://en.wikipedia.org/wiki/File:Yes_check.svg





























Blood Types

Recipient[1] Donor[1]

O− O+ A− A+ B− B+ AB− AB+ O− Y

O+ Y Y

A− Y Y

A+ Y Y Y Y

B− Y Y

B+ Y Y Y Y

AB− Y Y Y Y

AB+ Y Y Y Y Y Y Y Y






























White Blood Cells

• Help defend the body against invasion by pathogens, andthey remove toxins, wastes, and abnormal/damaged cells

• A typical µL of blood contains 6000-9000 WBCs. Comparethat to RBCs

• Most of the WBCs in the body at a given moment are in theconnective tissue proper or in organs of the lymphaticsystem

• Circulating WBCs are just a fraction of the total #

• Leukocytes (leuko=white,cyte=cell )

• All contain nuclei andorganelles unlike…

1



Types of WBCs

• Can be classified basedon the appearance ofgranules when viewedunder the lightmicroscope.

1. Granulocytes – Contain visible granules.

Includes:• Basophils

• Eosinophils

• Neutrophils

2. Agranulocytes – Do not contain visible

granules. Includes:• Lymphocytes

• Monocytes

1

2



WBC Circulation and Movement

• Use the bloodstreammainly to travel fromorgan to organ or toquickly go to areas ofinvasion/injury.

• Characteristics ofcirculating WBCs:

– Capable of amoeboid movement• What role might this play in WBC function?

– They can migrate out of the bloodstream by squeezing

thru endothelial cells (this process is called diapedesis) – They are attracted to specific chemical stimuli. This is

known as positive chemotaxis and allows WBCs toconverge on pathogens and damaged tissues

Granulocytes



Granulocytes -

Neutrophils• 50-70% of circulating WBCs

• Cytoplasm is packed with pale(“neutral colored”) granules thatcontain bactericidal compounds

• Mature neutrophils have asegmented nucleus. They are

a.k.a polymorphonuclearleukocytes.

• About 12µm in diameter.

• Highly mobile and generally thefirst WBCs to arrive at an injurysite.

• Specialize in attacking anddigesting bacteria that havebeen “marked” for destruction.

• Survive in the bloodstream foronly about 10hrs

Granulocytes



Granulocytes -

Eosinophils• 2-4% of circulating WBCs

• Similar in size to neutrophils but havereddish-orange staining granules (Eos isthe Greek goddess of dawn) and abilobed nucleus.

• Move into tissues after several hours and

survive from minutes to days.• They will phagocytize antibody-coated

bacteria, protozoa, and cellular debris,but their main method of attack is theexocytosis of toxic compounds onto thesurface of their target.

• Important defenders against large, multi-cellular parasites such as flukes orparasitic worms. They in #dramatically during a parasitic infection.

• Also sensitive to allergens and in #

during allergic reactions as well.

Granulocytes



Granulocytes -

Basophils

• >1% of circulating leukocytes• Smaller than neutrophils and

eosinophils, only about 8-10µmin diameter.

• Contain granules that appeardeep purple or blue

• Basophils migrate to injury sitesand discharge the contents oftheir granules – histamine (avasodilator and increaser of

capillary permeability) andheparin (an anticoagulant). Thisenhances the local inflammationinitiated by mast cells andattracts other WBCs

A l t



Agranulocytes -

Monocytes

• 2-8% of circulating WBCs

• Almost twice as big as anRBC

• Nucleus is large and tends

to be oval or kidney-shaped• Individual monocytes use

the bloodstream as ahighway, staying incirculation for only about24hrs before enteringperipheral tissues tobecome a tissuemacrophage, an aggressivephagocyte.

A l t



Agranulocytes -

Lymphocytes

• 20-30% of circulating leukocytes• Slightly larger than RBCs. In

blood smears, you typically onlysee a thin halo of cytoplasmaround a relatively large nucleus.

• Continuously migrate from thebloodstream thru peripheraltissues and back into thebloodstream.

• Circulating lymphocytes are only a minute fraction of the total #in the body. Most are in other connective tissues and in

lymphatic organs.• Circulating blood contains 3 classes:

– T cells: defend against foreign cells and tissues and coordinate the immuneresponse

– B cells: produce and distribute antibodies that attack foreign materials



WBCs in order of abundance:

Never (neutrophils Let (lymphocytes)

Monkeys (monocytes)

Eat (eosinophils)

Bananas (basophils)

How do I remember the

relative percentages?

60 + 30 + 6 + 3 +1(i.e., 60% neutrophils, 30%lymphocytes, 6% monocytes, 3%eosinophils & 1% basophils)

Platelets



Platelets

• Flattened disk-like cell fragments that are about 1µm by

4µm.

• Act as a participant in the vascular clotting system.

Platelets are sometimes referred to as thrombocytes

(thrombus=clot)

• Continuously being replaced. Each platelet circulates for

9-12 days before being removed by splenic phagocytes.

• On average there are350,000 platelets/µL ofblood.

• Produced in the bonemarrow. Large cellscalled megakaryocytes release fragments(platelets) into the

circulation.



Platelet Functions

• Transport of chemicalsimportant to the clottingprocess. By releasingenzymes and other factors,platelets help initiate the

clotting process• Formation of a temporarypatch (platelet plug) in thewalls of damaged bloodvessels.

• What do you supposethrombocytopenia is? What process would it impact?

Hemopoiesis = Leukopoiesis +



Hemopoiesis = Leukopoiesis +

Erythropoiesis + Thrombopoiesis

Hemocytoblast

Lymphoid Stem

Cell

Myeloid Stem

Cell

Erythrocyte

Megakaryocyte

Lymphocyte

Platelet

Where does all of this take place?

Hemostasis

http://www.hemophiliagalaxy.com/2_PROFESSIONALS/MEDICAL_EDUCATION/images/HEMOSTASIS3.gif



Hemostasis(Blood Clotting)

• Prevents blood loss thru the walls of

damaged blood vessels

• Also establishes a framework for further

tissue repairs

• 3 main phases:

– Platelet Phase

– Vascular Phase

– Coagulation Phase

http://www.hemophiliagalaxy.com/2_PROFESSIONALS/MEDICAL_EDUCATION/images/HEMOSTASIS3.gif



Platelet Phase

• Occurs within 15sec of the injury

• Platelets begin to attach to sticky endothelial cells, the basementmembrane, and to exposed collagen fibers.

• As platelets “stick,” they become “activated.” Activated plateletsrelease:

• The aggregation of platelets eventually results in a platelet plug, atemporary mass of platelets that stops blood loss and forms aframework for the clot.



Vascular Phase

• Lasts about 30 mins

• Endothelial cells at the injurysite undergo changes:

– Contract and expose theirbasement membrane to the

bloodstream – Release chemical factors

and local hormones – serotonin initiates spasms

– Endothelial cell membranes

become sticky

Blood Vessel Damage

Smooth muscle in BV wall

contracts – Vascular Spasm

BV diameter

Blood loss slows

C l i Ph



Coagulation Phase

• Begins 30sec or more after

vessel damage occurs (unlikethe first 2 phases which beginalmost immediately)

• Involves a sequence of stepsleading to the conversion of

fibrinogen (a circulating plasmaprotein) to the insoluble proteinfibrin.

• A network of fibrin grows andcovers the surface of the platelet

plug. RBCs and additionalplatelets are trapped in thistangle, forming a blood clot thateffectively seals the damagedvessel wall.



Clot Retraction

• Once the fibrin meshwork has appeared, RBCs

& platelets stick to the fibrin strands.

• The platelets then contract and the clot

undergoes clot retraction which: – Pulls the torn edges of the vessel closer together,

reducing residual bleeding and stabilizing the injury

site

– Reduces the size of the injured area, making iteasier for fibroblasts, smooth muscle cells, and

endothelial cells to complete repairs.



Manipulating Hemostasis

• Important anticoagulant drugs

include:

– Heparin Inactivates thrombin

– Coumadin Blocks the action ofVitamin K

– Streptokinase Converts

plasminogen to plasmin

– Aspirin Inhibits plateletaggregation



Thrombi & Emboli

• A thrombus is formed whenplatelets begin to stick to thewall of an intact blood vessel – Platelets are often attracted to

plaques – where endothelial andsmooth muscle cells contain lotsof lipids.

– What problems could a growingthrombus pose?

• If the clot (thrombus) breaksoff and begins to drift in thebloodstream, it is called anembolus. – What problems could an

embolus cause?

Above: Normal artery

Below: Same artery with a

large thrombus (arrow)

Hemophilia



Hemophilia• Refers to several different hereditary bleeding disorders

with similar signs/symptoms

• Hemophilia A – Results from lack of Factor VIII. Most common type (83%)

– X-linked

• Hemophilia B

– Less common. Due to deficiency of Factor IX

– Also X-linked

What symptoms do

you suppose arecharacteristic ofhemophiliacs?

206 blood.ppt revised ps

Documents