Human Anatomy & Physiology

Basic Anatomy & Physiology II Dr. L. Bacha

Chapter Outline (Marieb & Hoehn 6th ed)

16.1 The functions of blood are transport, regulation, and protection

There are three general functions of blood:

transport; regulation; protection

- please read the information on p. 554 to 555 about each of the functions of blood

16.2 Blood consists of plasma and formed elements

blood is a specialized type of connective tissue composed of:

1. formed elements - erythrocytes, leukocytes and platelets

2. plasma - the fluid extracellular matrix

a sample of blood can be spun in a centrifuge to separate out its components (see Fig. 16.1)

hematocrit is the percentage of the volume of whole blood contributed by erythrocytes

- a normal hematocrit value is about 45%

leukocytes and platelets contribute less than 1% of the volume of whole blood

plasma makes up most of the remaining 55% of the volume of whole blood

Physical Characteristics and Volume

blood is denser and more viscous (more sticky) than water

color of blood:

- what color is oxygen-rich blood? scarlet

- what color is oxygen-poor blood? dark red

blood is slightly alkaline, with a pH of ~ 7.4

the temperature of blood is 100.4°F (38°C)

- so, how does it compare to body temperature? slightly above

blood accounts for approximately what percent of body weight? 8%

what is the normal average volume of blood in adult males? 5 to 6 L

- what is the normal average volume of blood in adult females? 4 to 5 L

Blood Plasma

plasma is the straw colored liquid portion of blood; it consists of mostly water with over 100 different solutes (see Table 16.1):

90 % water

10 % solutes

- plasma proteins (8% by weight of plasma); most are synthesized by hepatocytes of the liver:

1.albumins - most abundant of the plasma proteins; play a role in maintaining osmotic pressure of the blood, which is important in total body fluid balance

2.globulins - transport lipids & fat-soluble vitamins; form antibodies

3.fibrinogen – a clotting factor; forms fibrin threads of a blood clot

- other solutes (2%) = nutrients, enzymes, hormones, electrolytes, gases, wastes, etc.

Formed Elements

the formed elements of blood are the erythrocytes, leukocytes, and platelets

read about the three unusual features that formed elements have!

16.3 Erythrocytes play a crucial role in oxygen and carbon dioxide transport

(A single drop of blood contains about 260 million RBCs!)Structural Characteristics of Erythrocytes

◦ erythrocytes are also called what? red blood cells (RBCs)

◦ they are small cells, about 7.5 μm diameter

◦ what are they shaped like?

biconcave discs – flattened discs with depressed centers

◦ 99% of formed elements are RBCs

◦ RBC count:

adult female: ~ 4.2 to 5.4 million RBCs per microliter (μL) or cubic mm of blood

adult male: ~ 4.7 to 6.1 million RBCs per microliter (μL) of blood

◦ the cytoplasm of erythrocytes contains mostly hemoglobin molecules; essentially no organelles

◦ the plasma membrane of RBCs:

- is strong and flexible, which allows the cells to fold so they can squeeze through capillaries of smaller diameter

- has glycolipids that are antigens, which account for different blood types

◦ three structural features of RBCs related to their ability to transport gases include:

1. small size and biconcave shape – provide a huge surface area for diffusion of O2 (and CO2) into and out of the RBC; also allows the cells to form stacks (like dinner plates)

2. lack of a nucleus and other organelles - allows more room for hemoglobin in the cytoplasm

3. lack mitochondria and produce ATP anaerobically, so they do not use the O2 that they carry

Functions of Erythrocytes

◦ RBCs contain hemoglobin (Hb; Hgb), which binds reversibly to O2 and CO2 to transport these gases in the blood; each erythrocyte has about 250 million hemoglobin molecules!

◦ normal hemoglobin content:

- about 13 - 18 grams per deciliter (100 mL) of whole blood in adult males; 12 - 16 g/dL in females

◦ structure of one hemoglobin molecule (see Fig. 16.4)

1. globin

- a globular protein that consists of what?

4 chains of polypeptides (2 alpha & 2 beta)

- CO2 binds to the amino acids of the globin, forming carbaminohemoglobin

2. heme unit (heme pigment) - a ringlike, nonprotein red pigment in the center of each polypeptide chain

- in the center of each heme unit is what?

an atom of iron

- the iron (Fe) in each heme can bind reversibly with one O2

so, a hemoglobin molecule can transport how many oxygens? four

one single red blood cell contains about how many hemoglobin molecules?

250 million

oxyhemoglobin forms when the oxygen binds to the iron of the heme

- blood containing RBCs filled with oxyhemoglobin is bright red, such as in systemic arteries and pulmonary veins

deoxyhemoglobin forms when oxygen is not bound to the iron of the heme

- blood containing RBCs filled with deoxyhemoglobin is dark red, such as in systemic veins and pulmonary arteries

Production of Erythrocytes

( Hematopoiesis (hemopoiesis) is blood formation; it occurs in the red bone marrow in adults, red bone marrow is found mainly in the bones of the axial skeleton, pectoral and pelvic girdles, and the proximal epiphyses of the humerus and femur red bone marrow contains immature blood cells, macrophages, and other cells as blood cells mature in the red bone marrow, they migrate through the thin walls of the sinusoids (large capillaries) to enter the bloodstream the various formed elements all arise from the same type of undifferentiated stem cell called a hematopoietic stem cell (hemocytoblast))

(“poiesis” is Greek for “production of”“hemato” means blood “erythro” means red)

Stages of Erythropoiesis

◦ erythropoiesis is the production of erythrocytes and it takes place in red bone marrow

- RBCs live about 120 days

- old or damaged RBCs are eliminated by phagocytic cells; new RBCs are produced at an equal rate to maintain normal numbers of RBCs

- erythropoiesis:

begins with a hematopoietic stem cell and involves cell division and differentiation of a series of cells (see Fig. 16.5):

near the end of erythropoiesis a precursor cell loses its nucleus and becomes a reticulocyte

the reticulocyte enters the bloodstream

after 1 to 2 days in circulation the reticulocyte becomes a mature RBC

- define reticulocyte (from the glossary in the back of the book)

an immature erythrocyte

- reticulocyte count

- provides a rough index of the rate of erythropoiesis

- normal reticulocyte count: ~ 1 – 2 % of erythrocytes in the blood are reticulocytes

- a low reticulocyte count in a person who is anemic might indicate a shortage of erythropoietin or an inability of the red bone marrow to respond to erythropoietin

- a high reticulocyte count might indicate a good red bone marrow response to anemia

Regulation and Requirements for Erythropoiesis

about 1% of circulating RBCs are replaced each day!

more than 2 million new RBCs are produced each second!

Hormonal Controls of Erythropoiesis

erythropoietin = a hormone produced by cells of the kidneys (and liver)

target: red bone marrow

effect: stimulates erythropoiesis

normally a continuous, moderate amount of erythropoietin is produced to keep the rate of production of RBCs in balance with the rate of destruction of RBCs

an increase in the release of erythropoietin occurs in response to hypoxia

e.g. if low O2 in the blood (hypoxia) is detected by cells in the kidney the kidneys produce more erythropoietin stimulates increased erythropoiesis in the red bone marrow increased number of RBCs are produced

Dietary Requirements for normal RBC production

iron - essential for hemoglobin synthesis

vitamin B12 and folic acid - necessary for normal DNA synthesis

Fate and Destruction of Erythrocytes

red blood cells have a useful life span of about how many days?

100 to 120 days

old or damaged RBCs are recognized and phagocytized by macrophages in the liver, spleen and bone marrow; after phagocytosis, hemoglobin is split into:

1. globin – is broken down into amino acids that are reused for protein synthesis

2. heme unit - is broken down into:

iron – bound to protein and stored for reuse

noniron portion of the heme unit – is degraded to bilirubin, which is released into the blood and binds to albumin

when the bilirubin bound to albumin circulates within the liver, bilirubin is secreted by hepatocytes of the liver into bile, which passes into the small and large intestine

bacteria in the large intestine convert bilirubin in bile to urobilinogens and stercobilinogens

most is excreted from the large intestine in the feces.

Erythrocyte Disorders

Anemias

- define anemia:

= a condition in which the blood’s oxygen-carrying capacity is too low to support normal metabolism

Anemia can be due to:

1) low numbers of RBCs (due to blood loss, not enough RBCs produced, too many RBCs destroyed

2) low hemoglobin content or abnormal hemoglobin in the RBCs

Polycythemia

- define polycythemia:

= is an abnormal excess of erythrocytes that increases blood viscosity, causing it to sludge, or flow sluggishly

16.4 Leukocytes defend the body

General Structural and Functional Characteristics of Leukocytes

what are leukocytes also called? white blood cells (WBCs)

characteristics of WBCs:

1. they can migrate out of the bloodstream by diapedesis, meaning that they are able to squeeze between the endothelial cells of blood capillaries into surrounding tissues

2. once out of the bloodstream, leukocytes move through the tissue spaces by what?

amoeboid moment

3. they are attracted by chemicals released by damaged cells or other leukocytes; this phenomenon is called positive chemotaxis

4. some (neutrophils, eosinophils, and monocytes) are capable of phagocytosis

in general, WBCs function in immunity

WBCs have a nucleus and do not contain hemoglobin

list the two major categories of leukocytes:

granulocytes and agranulocytes

Granulocytes

list the three types of granulocytes:

neutrophils, eosinophils, basophils

granulocytes are larger than erythrocytes, have conspicuous granules in the cytoplasm after staining, and generally have a lobed nucleus; they are produced in red bone marrow

1. Neutrophils

∙ comprise 50-70% of all leukocytes in humans

∙ 10 to 12 µm diameter

∙ pale cytoplasm speckled with very fine lavender granules

∙ polymorphic nucleus (3 - 6 lobes); looks like sausage links!

- why are neutrophils often called polymorphonuclear leukocytes (PMNs)?

- because of nuclear variability (“many shapes of the nucleus”)

∙ function: phagocytic, especially phagocytize bacteria and some fungi; they respond first, before other WBCs during inflammation

2. Eosinophils

∙ comprise 2 to 4% of all leukocytes

∙ 10 to 12 µm diameter

∙ nucleus is polymorphic, often bilobed; their cytoplasmic granules stain a shade of red

∙ functions: release enzymes that reduce the inflammation during allergic reactions; phagocytize antigen-antibody complexes; destroy certain parasitic worms

3. Basophils

∙ comprise only 0.5 to 1% of all leukocytes

∙ 8 to 10 µm diameter

∙ irregularly shaped nucleus, often obscured by basophilic cytoplasmic granules of various sizes

∙ their cytoplasmic granules release histamine and heparin:

- histamine is an inflammatory chemical that acts as what and attracts what?

- acts as a vasodilator

- attracts other white blood cells to the inflamed site

- heparin is an anticoagulant

Agranulocytes

list the two types of agranulocytes:

lymphocytes and monocytes

agranulocytes lack visible cytoplasmic granules

they are produced in red bone marrow and lymphatic tissue

1. Lymphocytes

∙ comprise 25% of all leukocytes

∙ 5 to 17 µm diameter

∙ most are small cells with a darkly stained, round or slightly indented nucleus surrounded by a thin rim of robin's egg blue cytoplasm

∙ function: there are three types of lymphocytes (T cells, B cells, and natural killer cells) that play a role in immunity

2. Monocytes

∙ comprise 3 to 8% of all leukocytes

∙ 12 to 20 µm diameter

∙ nucleus is variable in shape (oval, kidney or horse-shoe) and usually eccentric

∙ cytoplasm is pale, gray-blue and frequently vacuolated

∙ function: migrate out of the blood into surrounding connective tissue and differentiate into macrophages, which phagocytize bacteria and debris

Production and Life Span of Leukocytes

define leukopoiesis:

= the production of white blood cells

see Fig. 16.11 that shows the formation of leukocytes, beginning with a hematopoietic stem cell

Leukocyte Disorders

normal WBC count = 5,000 to 10,000 WBCs per microliter of blood

define leukocytosis ( from the glossary in the back of the book):

= an increase in number of leukocytes

- e.g., due to bacterial infection

define leukopenia (back to p.654):

= an abnormally low WBC count

- some causes of leukopenia include drugs, particularly glucocorticoids and anticancer agents

what does the term leukemia refer to?

a group of cancerous conditions involving overproduction of abnormal WBCs

16.5 Platelets are cell fragments that help stop bleeding

platelets, also called thrombocytes, are cytoplasmic fragments of extraordinarily large cells in

the bone marrow called what?

(Platelets are also called thrombocytes.Why is “thrombocyte” not an appropriate name?)megakaryocytes

platelets are 2 to 4 µm; disc shaped; pale blue cytoplasm with fine granules

the granules contain an impressive array of chemicals that act in the clotting process

- list the chemicals that platelets contain:

serotonin, Ca+2, a variety of enzymes, ADP,

and platelet-derived growth factor (PDGF)

in the bone marrow, megakaryocyte sends cytoplasmic extensions into sinusoids; these extensions break apart, releasing platelets into the blood flowing through the sinusoids

normal range of platelets in the blood = 150,000 to 400,000 platelets per microliter of blood

Before we cover hemostasis, jump to Chapter 18 p. 609-610 !!!

PART 1

BLOOD VESSEL STRUCTURE AND FUNCTION

List the three major types of blood vessels: arteries, capillaries, veins

which vessels carry blood away from the heart, arteries or veins? arteries

which vessels carry blood toward the heart, arteries or veins? veins

18.1 Most blood vessel walls have three layers

the walls of most blood vessels have three layers, or tunics, that surround a central blood-containing space called what? the vessel lumen

examine Fig. 18.2 and identify the 3 tunics that form the wall of an artery

1. Tunica Intima - innermost layer of a blood vessel wall; it contains :

a. the endothelium

- define endothelium:

= simple squamous epithelium that lines the lumen of all vessels

- its flat cells fit closely together, forming what?

- a slick surface that minimizes friction as blood moves through the lumen

b. small amount of underlying loose connective tissue

c. internal elastic lamina (only in arteries, not veins)

2. Tunica Media - middle layer of a blood vessel wall

∙ it is mostly what?

- circularly arranged smooth muscle cells and sheets of elastin

∙ the activity of the smooth muscle is regulated by what by?

- sympathetic vasomotor nerve fibers of the autonomic nervous system and a whole battery of chemicals

∙ define vasoconstriction:

= lumen diameter decreases as the smooth muscle contracts

∙ define vasodilation:

= lumen diameter increases as the smooth muscle relaxes

∙ small changes in vessel diameter greatly influence what?

blood flow and blood pressure

3. Tunica Externa - the outermost layer of a blood vessel wall

∙ it is composed largely of loosely woven collagen fibers that do what?

- protect and reinforce the vessel, and

- anchor it to surrounding structures

∙ what are the tiny blood vessels called that nourish the more external tissues of the wall of larger blood vessels? the vasa vasorum

Now jump back to Chapter 16 page 569:

16.6 Hemostasis prevents blood loss

define hemostasis ( from the glossary in the back of the book):

= the stoppage of bleeding

list the three steps of hemostasis that occur in rapid sequence (and see in Fig. 16.13):

1. vascular spasm 2. platelet plug formation 3. coagulation (bld clotting)

Step 1: Vascular Spasm

damage to a blood vessel triggers a local contraction of the smooth muscle cells of the vessel wall called vascular spasm; this contraction results in vasoconstriction

list factors that trigger vascular spasm:

- direct injury to vascular smooth muscle

- chemicals released by endothelial cells and platelets

- reflexes initiated by local pain receptors

why is the spasm response valuable?

because a strongly constricted artery can significantly reduce blood loss for 20 – 30 min, allowing time for the next two steps to occur

Step 2: Platelet Plug Formation

as a rule, platelets do not stick to each other or to the smooth endothelial linings of blood vessels; intact endothelial cells release what two chemicals?

nitric oxide and prostaglandin called prostacyclin

- both chemicals prevent and restrict what?

- prevent platelet aggregation in undamaged tissue and restrict aggregation to the site of injury

when the endothelium is damaged and underlying collagen fibers are exposed, the following occurs:

platelet adhesion: platelets contact and stick to the collagen fibers that are

now exposed below the endothelium of the damaged blood vessel

as platelets arrive in the area of a damaged vessel, they become activated;

the activated platelets:

1. swell and form spiked cytoplasmic processes that extend toward other platelets

2. become stickier

3. release a wide variety of chemicals

- list the chemical messengers that activated platelets release and indicate the function of each:

adenosine diphosphate (ADP) – a potent aggregating agent that causes more platelets to stick to the area and release their contents

serotonin and thromboxane A2 – enhance vascular spasm and platelet aggregation

as more and more platelets arrive, they release more chemicals, they stick to one another more, etc; buiding an aggregation of platelets called a platelet plug, which further decreases blood loss

Step 3: Coagulation

coagulation is also called what? blood clotting

coagulation involves a complex sequence of steps that leads to the conversion of circulating fibrinogen into insoluble strands of the protein called fibrin (see Fig. 16.14) and results in the formation of a blood clot; it is complete in about 3 to 6 minutes after blood vessel damage

a blood clot consists of a network of fibrin threads and trapped formed elements (Fig. 16.15)

clotting involves 13 clotting factors (I to XIII) (see Table 16.3)

∙ these factors include calcium ions and 12 different proteins (mostly synthesized by hepatocytes of the liver, some are synthesized by platelets or they are also released by damaged tissues)

( We will summarize the three phases in class so leave the spaces next to the phases blank for now!)

3 PHASES OF BLOOD CLOTTING

Phase 1:

There are two pathways that lead to the formation of prothrombin activator:

The Extrinsic Pathway

- the formation of prothrombin activator is initiated by a tissue protein outside of the blood that leaks into the blood from damaged cells outside of blood vessels

The Intrinsic Pathway

- the formation of prothrombin activator is initiated by activators within the blood (damaged endothelial cells exposed to underlying collagen or damaged platelets)

∙ both pathways require calcium ions

( the “common pathway”)Phase 2:

Phase 3:

∙ the fibrin molecules then polymerize (join together) to form insoluble fibrin threads

(Is serum the same as plasma?!No! Serum is similar to plasma but serum lacks clotting factors.)∙ the fibrin threads form a meshwork that traps formed elements and forms the structural basis of the blood clot

serum is plasma without clotting factors

Clot Retraction and Fibrinolysis

Clot Retraction

- once a clot forms, platelets contract and pull on the fibrin threads, which compacts the clot and draws the edges of the damaged vessel closer together

vessel repair: while clot retraction is occurring, the vessel is healing:

- name the substance that is released by platelets that stimulates smooth muscle cells and fibroblasts to divide and rebuild the wall of the vessel:

- platelet-derived growth factor (PDGF)

- meanwhile, endothelial cells multiply and restore the endothelial lining of the vessel

(lysis means to rupture, so fibrinolysis is the digestion of fibrin, which forms the meshwork of the clot)Fibrinolysis

what does fibrinolysis remove?

unneeded clots when healing has occurred

plasminogen (an inactive enzyme incorporated into the blood clot) is activated

by tissue plasminogen activator (tPA) to plasmin (fibrinolysin)

- plasmin (fibrinolysin) is an active enzyme that digests the fibrin of a clot

what cells secrete tissue plasminogen activator? endothelial cells

Factors Limiting Clot Growth or Formation

Factors Limiting Normal Clot Growth

list the two homeostatic mechanisms that prevent clots from becoming unnecessarily large:

(1) swift removal of clotting factors

(2) inhibition of activated clotting factors

for clotting to occur, the concentration of activated clotting factors must reach certain critical levels

read about why don’t clots usually form in rapidly moving blood

(substances in the blood that remove or inactivate “extra” thrombin so that more fibrinogen cannot be converted to fibrin; this prevents continued, unnecessary enlarging of the blood clot) antithrombin III

heparin

Factors Preventing Undesirable Clotting

a smooth and intact endothelium, and also substances secreted by the endothelial cells (nitric oxide and prostacyclin), normally prevent platelet adhesion

Disorders of Hemostasis

⦁ Thromboembolic Disorders (conditions that cause unwanted clot formation)

Thrombi and Emboli

define a thrombus:

= a clot that develops and persists in an unbroken vessel

if the thrombus breaks away from the vessel wall and floats freely in the bloodstream, it becomes an embolus

unwanted clotting can be initiated by:

1. roughening of the endothelium (such as with atherosclerosis; infection), which allows platelets to aggregate

2. slowly flowing blood – allows clotting factors to accumulate

thrombolytic agents are substances administered to patients to dissolve unwanted blood clots that have formed e.g., tissue plasminogen activator (tPA) and streptokinase

Anticoagulant Drugs

a number of drugs, most importantly what three, are used clinically to prevent undesirable clotting in patients at risk for heart attack or stroke?

aspirin, heparin, and warfarin

- what does aspirin inhibit and block?

inhibits thromboxane A2 formation

(blocking platelet aggregation and platelet plug formation)

- heparin- the injectable anticoagulant most used in hospitals

- warfarin (Coumadin) interferes with the action of vitamin K used by the liver to synthesize some of the clotting factors

- EDTA and citric acid – remove calcium ions to prevent blood from clotting in a test tube

⦁ Bleeding Disorders (conditions that cause abnormal bleeding)

- anything that interferes with the clotting mechanism can result in abnormal bleeding

- the two most common causes of abnormal bleeding are:

1. platelet (thrombocyte) deficiency

what is the term for platelet deficiency? thrombocytopenia

2. deficits of some clotting factors, which can result from what?

impaired liver function or genetic conditions, such as hemophilia

impaired liver function can result in abnormal bleeding if the liver is unable to synthesize clotting factors

hemophilia refers to several hereditary bleeding disorders that result from deficiency of certain clotting factors

16.7 Transfusion can replace lost blood

in what two ways can the human cardiovascular system minimize the effects of blood loss?

(1) by reducing the volume of the affected blood vessels

(2) by stepping up production of red blood cells

blood losses of 15 to 30% cause what?

pallor and weakness

loss of more than 30% of blood volume results in what?

severe shock, which can be fatal

Transfusing of Red Blood Cells

- name the two types of transfusions and summarize when each is used:

whole blood transfusions – rarely used – only when blood loss is rapid and substantial

infusions of packed red blood cells – for restoring oxygen-carrying capacity

Human Blood Groups

∙ The surfaces of erythrocytes contain a genetically determined assortment of glycoproteins and glycolipids that serve as antigens (Ag; agglutinogens)

∙ The basis of blood groups is the presence or absence of the different types of antigens on the surface of red blood cells.

∙ There are two main blood groups: ABO and Rh

ABO Blood Group

the ABO blood group is based on the presence or absence of what two antigens (agglutinogens)?

type A and type B

the two types of preformed antibodies in the plasma are anti-A and anti-B antibodies (agglutinins)

- do you think that people normally have antibodies that react with antigens on their own RBCs? no

Examine Table 16.4:

- what are the four possible blood types in the ABO blood group? A, B, AB, O

we will fill in the chart belolw in class to characterize the RBCs and plasma of each blood type in the ABO blood group:

BLOOD TYPE

A

B

AB

O

Antigens present on

RBCs

A antigens

B antigens

A and B antigens

no A antigens

no B antigens

Antibodies present in

Plasma

anti-B antibodies

anti-A antibodies

no anti-A or anti-B antibodies

anti-A and anti-B antibodies

can receive RBCs from this/these donor(s):

Rh Blood Groups

why is it named “Rh”?

originally identified in rhesus monkeys

there are many different types of Rh antigens, but the D antigen is a main one and is referred to as the Rh antigen (Rh factor)

what it means to be ”Rh “positive” and Rh “negative” is summarized in the table below:

Rh +

Rh -

Rh antigens on RBCs

no Rh antigens on RBCs

no anti-Rh antibodies in the plasma

no anti-Rh antibodies in the plasma

UNLESS previously exposed to the

Rh antigen; then the person’s immune system produces anti-Rh antibodies

- read the information on pages 576 to 577 on transfusion reactions,

blood typing, restoring blood volume, and diagnostic blood tests

(even though you won’t be tested on it…!)

The End!

15

Ch 16 L's Blood 6th ed