anatomy of blood part 2 &3

7/29/2019 Anatomy of blood part 2 &3

1/55

The Cardiovascular System:Blood


2/55

The CV System

cardiovascular system

consists of three interrelated components:

Blood

Heart

Blood vessels.


3/55

Blood

Hematology

The study of blood, blood forming tissues, and the

disorders associated with them

Blood contributes to homeostasisby:

Transporting respiratory gasses, nutrients, and

hormones to and from your bodys cells.

Helping to regulate body pH and temperature.

Providing protection through its clotting

mechanisms and immune defenses.


4/55

Characteristics of Blood

Blood is more dense and viscous (thicker) than water.

Has a temperature of 38 deg C

1 deg C higher than oral or rectal body temp

Slightly alkaline

pH ranging from 7.35 7.45

Changes from dark to bright red depending on oxygen content

Plasma volume constitutes roughly 25% of extracellular fluid (ECF)

Other 75% of ECF is interstitial fluid (ISF)

Average blood volume in:

Males = 5 to 6 liters (~1.5 gal)

Females = 4 to 5 liters (~1.2 gal)

Difference mainly due to body size


5/55

Blood

Blood is a type of connective tissue

Composed of:

Plasma

Formed elements

Interstitial fluid (ISF)

Fluid that bathes body tissues

Constantly renewed by blood

Discussed in more detail during blood vessels and

hemodynamics lecture


6/55

Components of Blood

Plasma

A watery liquid extracellular matrix that containsdissolved substances.

~91.5% water and 8.5% solutes The majority of the solutes in plasma are protiens

Specific proteins confined blood are called plasma proteins

Most of the plasma proteins are produce by the liver

These proteins have many functions but a very important

one is a contribution to the maintenance of proper bloodosmotic pressure

Other solututes include electrolytes, nutrients, gasses,regulatory substances, and waste products


7/55


8/55


9/55

Components of Blood

Formed Elements

3 principal components

Red Blood Cells (RBCs)

White Blood Cells (WBCs)

Platelets


10/55

Formed Elements

Hemopoiesis (hematopoiesis)

Process by which the formed elements of blood develop

From late fetal development to death, red bone marrow isthe primary site of hemopoiesis

All Blood cells arise from pluripotent stem cells found within thered marrow

The pluripotent stem cells give rise to 2 types of stem cells: Myeliod andlymphoid stem cells

Lymphoid cells are named so due to their beginning development inthe red bone marrow and ending in the lymphoid tissue

Some of the myeloid stem cells give rise to progenitor cells

The other myeloid stem cells, lymphatic stem cells, and progenitor cellsgive rise to precurser cells (blasts) which then differentiate into the bloodcells


11/55


12/55

Regulation of Hemopoiesis

Hemopoietic growth factors

Hormones that regulate the differentiation and proliferation ofparticular progenator cells

Erythropoietin (EPO) increases the # of RBC precursers EPO is primarily produced cells in the kidneys

Renal failure leads to RBC defficiency

Exogenous or synthetic EPO is also a banned substance in most professional sports

Thrombopoetin (TPO) stimulates formation of platelets frommegakaryocytes

TPO is produced by the liver

Cytokines small glycoproteins that regulate the development of differentblood cells

Typically produced by cells such as red bone marrow cells, leukocytes, macrophages,

fibroblasts, and endothelial cells Laboratory made hemopoietic growth factors have shown great

promise in helping reduce some of the side effects of chemotherapyas well as treatment of particular disieases and genetic defficiencies


13/55

Formed Elements


Also called erythrocytes

make up the bulk of the blood cells Hematocrit = the % of RBCs per unit blood volume

Normal Hct is around 45% bi-concave discs

Allows for high surface area which is optimal forgas exchange

Also allows RBCs to deform without rupturing Very important in capillary circulation

Amongst many other membrane proteins, theRBC membrane contains glycolipid surfacemarkers that designate ABO Rh blood type


14/55


Developing RBCs lose their nucleus and many otherorganelles as they mature

When a maturing RBC loses its nucleus, it becomes a reticulocyte

The mature form is highly specialized for oxygen transport Due to the lack of most organelles, the majority of their internal

space is available for oxygen transport

Cytosol of mature RBCs contain a high amount of hemoglobin ~33% of the cells weight

Each RBC contains about 280 million hemoglobin molecules

Hemoglobin (Hgb) is a protein molecule adapted to carry O2 (andCO2 as well)

A Hgb molecule consists of 4 large globin proteins (2 alpha and 2 betachains), each embedding an iron-containing heme center

The iron binds oxygen


15/55


Lack mitochondria

Generate ATP anaerobically so they do not use up the oxygen beingtransported

As previously stated, mature RBCs lack a nucleus or any proteinmaking machinery

This means they cannot synthesize new components to repair damaged ones Thus they are destined to die

Average RBC life is about 120 days.

~1% of RBCs must be destroyed and replaced every day

250 billion cells per day!

Old RBCs a subject to bursting when passing through the narrow channels inthe spleen

Ruptured RBCs are removed from circulation and destroyed by fixed phagocytoticmacrophages in the spleen and liver

Some of the breakdown products are recycled and others are excreted as shown in thefollowing slide

In a sense, mature RBCs are not really cells, but remnants of cells witha very specific purpose to carry O2to the tissues of the body


16/55


17/55

Abnormalities of Erythropoiesis

Anemia A condition of insufficient RBCs or hemoglobin (quality or

quantity) It is most often the result of low iron intake, hemolysis,

autoimmune disease, blood loss, or lack of production in the

bone marrow Polycythemia

a condition of excess number of RBCs per unit volume It occurs in response to:

Hypoxia Condition in which the body or a region of the body is deprived of an

adequate oxygen supply

Blood doping - receiving a transfusion of RBCs right before asporting event to increase the bloods oxygen carrying capacity

Natural blood doping is training at high altitude shots of EPO (illegal doping) smoking (COPD) dehydration


18/55

Anemias

Iron deficiency anemia is the most common

anemia in the U.S., and affects primarily

menstruating women In the United States, 20% of all women of

childbearing age have iron deficiency anemia,

compared with only 2% of adult men

Hemorrhagic anemia is the result of

precipitous blood loss, and results in an equal

decrease in Hct, Hgb content, and RBC count


19/55

Anemias

Sickle-cell disease (SCD) also called sickle-cell anemia An autosomal recessive disorder.

A genetic defect in the primary DNA sequence leads toproduction of a faulty Hgb chain, and RBCs that takeon a rigid, sickle-shape

People who only have one sickle-cell gene mayexperience mild symtoms

People who have two copies of the sickle-cell genemay experience severe symptoms

Sickling decreases the cells' flexibility and resultsin a variety of complications;

Decreased oxygen carrying capacity Easily ruptured RBCs Increased risk of stroke

life expectancy is shortened Many others

May confer an advantage in malaria proneenvoronments

People who inherit one copy of the mutated sickle-cellgene show increased resistance to infection and effectsof the plasmodium parisite

http://en.wikipedia.org/wiki/File:Sickle_cell_

01.jpg


20/55

Next Lecture

Lecture 1 part 2: Blood


21/55

Formed Elements

White Blood Cells (WBCs)

Also called leukocytes

Function in immunity and defense

Have nuclei and a full complement of other organelles

do not contain the protein Hgb

divided into two groups depending on whether they

contain conspicuous chemical-filled cytoplasmic

granules (when stained)

Granulocytes

Agranulocytes


22/55

Leukocytes

Phagocytosis the process of engulphing a substanceor another cell Monocytes (later termed macrophages when they

differentiate) and neutrophills are active phagocytes Chemicals released by microbes and inflamed tissues

attract phagocytes, a phenomenon called chemotaxis This graphic shows a PMN

phagocytizing (ingesting) amicrobe for internaldigestion and destruction


23/55

Granulocytes

Neutrophil Also termed the polymorphonucleocyte

(PMN)

The most numerous WBC in normal blood(60-70% of circulating white cells)

PMNs are granulocytes with a pinkishcytoplasm

one of the two major phagocytes in thebody

their principal role is to fight bacterialinfections

Use a variety of chemicals destroypathogens

Lysozyme (hydrolytic enzymes), superoxideanion (O2

-), hydrogen peroxide, hypochloriteanion (much like bleach)


24/55

Granulocytes

Eosinophils Characterized by their large red

granules

Involved in mediation of

inflammation and phagocytosis ofantigen-antibody complexes

They are much less numerous thanneutrophils (2-4% of circulatingWBCs)

However, their numbers increaseslightly with parasitic infection

they have also been associated with thedevelopment ofallergies


25/55

Granulocytes

Basophils Contain large, dark blue,

histamine containing granules

Normally, they are the lowestnumber of circulating WBCs

(only 0-1%),

Play an important role in the

escalation ofinflammatoryresponses


26/55

Agranulocytes

Monocytes

Arise from the same immediate precursor cell as the 3

granulocytes (the myeloid stem cell)

Along with neutrophils, monocytes are the other major group of

phagocytic cells. Constitute only 3-8% of the

circulating WBCs

Differentiate into Macrophages in tissues

Some become fixed (localized to a

particular tissue) and others become

wandering (roamers that congregate at

sites of infection or inflammation)


27/55

Agranulocytes

Lymphocytes Do not have granules or phagocytize

The major soldiers in immune system battles

Approximately 20-30% of circulating white cells

Lymphocytes are the cornerstone of the specific immuneresponse

Continuosly move between blood and

lymphatic tissue Only spend up to a few hours at a

time in blood Develop into;

T-cells

B-cells

Natural killer cells


28/55

Leukocyte Movement

Emigratrion

Formally calleddiapedesis

The process by whichWBCs leave the bloodstream

Usually due to a signal

from infection orinflammation of thatparticular region ortissue


29/55

WBC Indices

WBCs are far less numerous than RBCs in the blood

For diagnostic purposes, physicians measure the totalnumber of circulating WBCs

Normal concentration ~5,000-10,000 cells/ml

Leukocytosis

Increase in WBC count above 10,000 cells/ml

Normal protective response due to stresses such as microbialinfection, strenuous exercise, anesthesia , and surgery

Leukopenia

WBC count less than 5,000 cells/ml

usually indicates a severe disease (AIDS, bone marrow failure,severe malnutrition, or chemotherapy)


30/55

WBC Indices

To enhance the diagnostic value of a WBC count,the percentages of each of the 5 types of WBCs isdetermined by using a machine to do a statisticalanalysis of the blood sample. This is called aWBC differential.


31/55

WBC Indices

Shifts in the normalpercentages of circulatingWBCs will often point towardsa bacterial infection (elevated

percentage of neutrophils) or aviral infection (elevatedpercentage of lymphocytes

In this peripheral blood smear a

patient with lymphocyticleukemia has a WBC >150,000and 90% of the WBCs arecancerous lymphocytes! Lymphocytic leukemia.


32/55


33/55

Formed Elements

Platelets Also called thrombocytes

Derived from megakaryocytes that splinter into 2000-3000fragments

Normal range = 150,000 400,000 platelets/ml

Have many vesicles but are anucleate (no nucleus) Short life span

5 9 days

Form a platelet plug in damaged vessels and release chemicalsthat promote clotting


34/55


35/55


36/55

Hemostasis

Hemostasis

The sequence of responses that halts bleeding

When blood vessels are damaged or ruptured, thehemostatic response must be quick, localized to theregion of damage, and carefully controlled in order tobe effective

Requires clotting factors, and substances released byplatelets and injured tissues

Three mechanisms reduce blood loss1. Vascular spasm2. Formation of a platelet plug3. Blood clotting (coagulation)


37/55

Vascular Spasm

Vasoconstriction of damaged blood vessel

Triggered by

Direct injury to vascular smooth muscle

Chemicals released by endothelial cells (cells that

line blood vessels) and platelets

Pain reflexes


38/55

Formation of a Platelet Plug

Positive feedback cycle

Damaged endothelium exposes collagen fibers

Platelets stick to collagen fibers via plasma protein

von Willebrand factor Swell, become spiked and sticky, and release

chemical messengers

ADP causes more platelets to stick and release their

contents Serotonin and thromboxane A2 enhance vascular spasm

and platelet aggregation


39/55

Coagulation

Reinforces platelet plug with fibrin threads

Thrombin: an enzyme that converts freefibrinogen (soluble) in the blood to fibrin threads

(insoluble) Blood transformed from liquid to gel-like

substance

Series of reactions that use clotting factors

# I XIII; most plasma proteins

Vitamin K needed to synthesize 4 of them

Figure 17.13 Events of hemostasis. Slide 1


40/55

2013 Pearson Education, Inc.

Step 1 Vascular spasm

Smooth muscle contracts,

causing vasoconstriction.

Step 2 Platelet plug

formation

Injury to lining of vessel

exposes collagen fibers;platelets adhere.

Platelets release chemicals

that make nearby platelets

sticky; platelet plug forms.

Step 3 Coagulation

Fibrin forms a mesh that traps

red blood cells and platelets,

forming the clot.

Collagenfibers

Platelets

Fibrin


41/55

Clot Retraction

Clot retraction is the consolidation of the

fibrin clot. As the clot retracts, it pulls the

edges of the damaged vessel closer together,

decreasing the risk of further damage Actin and myosin in platelets contract

Stabilizes clot

new endothelial cells can then repair the vessellining


42/55

Fibrinolysis

Because blood clotting involves amplification and

positive feedback cycles, a clot has a tendency to

enlarge, creating the potential for impairment of blood

flow through undamaged vessels The fibrinolytic system dissolves small, inappropriate clots

It also dissolves clots at a site of damage once the damage is

repaired

Both body tissues and blood contain substances that can

activate plasminogen to become plasmin, (the enzyme

that actively dissolves clots)


43/55

Intravascular Clotting

Clotting in an unbroken blood vessel (usually avein) is called thrombosis; the clot itself,called a thrombus

Embolus: thrombus freely floating in bloodstream Embolism: embolus obstructing a vessel

E.g., pulmonary and cerebral emboli

Blocks blood supply to region and can result in tissuedeath

Risk factors atherosclerosis, infection,inflammation, slowly flowing blood or blood stasisfrom immobility


44/55

Anticoagulant Drugs

Aspirin

Antiprostaglandin that inhibits thromboxane A2

Heparin

Anticoagulant used clinically for pre- and postoperativecardiac care

Helps antithrombin block thrombin formation and activity

Thrombin is involved in fibrin clot formation

Warfarin (Coumadin)

Interferes with action of vitamin K

Works slower than heparin

Dabigatran directly inhibits thrombin


45/55

Next Lecture

Lecture 2 part 3: Blood type


46/55

Blood Transfusion

Blood transfusion The process of transferring blood or blood products from

one person to another Almost all donated blood in the U.S. is separated into

its various components to make better use of it Whole blood is fractionated into units of;

Packed red blood cells (PRBCs) Fresh frozen plasma (FFP) Platelets WBCs

Albumin, coagulation factors, and antibodies can beindividually collected

Serum - serum is just plasma without the clottingfactors


47/55

Antigens and Antibodies

Red cells (and all cells in the body) have antigens ontheir surface which act as surface markers

Antigens can be;

Proteins

Glycolipids = carbohydrate + lipid Glycoprotiens = carbohydrate + protein

Proteolipids = protein + lipid

Anything perceived as foreign; generates an immuneresponse

Antigens on foreign cells and particles generate these responses

Promoters of agglutination (clumping); called agglutinogens

Thus antigens are also called agglutinogens


48/55

Antigens and Antibodies

Antibody

Proteins produced by B-cells that are used by the

immune system for identification and destruction

of foreign objects Each antibody type is very specific for a particular

antigen

Antibodies are also called agglutinins


49/55

Human Blood Groups

Types A, B, AB, and O Based on presence or absence of two

agglutinogens (A and B) on surface of RBCs

Blood may contain preformed anti-A or anti-Bantibodies (agglutinins) Act against transfused RBCs with ABO antigens not

present on recipient's RBCs

For instance, those with A antigens on their red

cells have anti-B antibodies in their serum Anti-A or anti-B form in blood at about 2 months

of age; adult levels by 8-10


50/55


51/55


52/55

Blood Groups

Blood typing for ABO

status is done using

single drops of blood

mixed with differentantisera Agglutination with an

antisera indicates the

presence of that

antigen on the RBC


53/55

Human Blood Groups

Rh antigen Named due to its discovery in the blood of the Rhesus monkey

Those with the Rh antigen are said to be Rh+ (positive)

Those without the Rh antigen are Rh- (negative)

Rh incompatibility can cause problems with any bloodtransfusion, so it is screened just as carefully as the ABO group

Anti-Rh antibodies not spontaneously formed in Rhindividuals Anti-Rh antibodies form if Rh individual receives Rh+ blood, or

Rh mom carrying Rh+ fetus

Second exposure to Rh+ blood will result in typicaltransfusion reaction


54/55

Transfusion Reaction

Occur if mismatched blood infused

Donor's cells

Attacked by recipient's plasma agglutinins

Agglutinate and clog small vessels Rupture and release hemoglobin into bloodstream

Result in

Diminished oxygen-carrying capacity Diminished blood flow beyond blocked vessels

Hemoglobin in kidney tubules renal failure

Table 17.4 ABO Blood Groups


55/55

anatomy of blood part 2 &3

Documents