CH 32--Red Blood Cells, Anemia, and Polycythemia & CH 33--Resistance of the Body to Infections Leukocytes, Granulocytes, Monocyte- Macophage System and Inflammation

Question 1

Red Blood Cells (Erythrocytes)
• RBCs are the most abundant cells in the blood.
• Needed to transport O2 from the lungs to the tissues via _____________
• Contain large quantities of ______ __________, an
enzyme that accelerates the reaction between CO2 and
carbonic acid (H2CO3) by several thousand-fold to form
bicarbonate (HCO3-) which carries CO2 (a metabolic
waste product) from the tissues to the lungs to be
expired.
• _____, like most proteins, is an acid-base buffer therefore, RBCs are responsible for contributing to the acid-base buffering of whole blood.

Answer 1

hemoglobin (Hb).

carbonic anhydrase

Hb

Question 2

The shape of the red blood cell can change significantly as it can squeeze through some tight spaces in circulation. It is considered a “bag” that can be deformed into almost any shape without rupturing.

Answer 2

know

Question 3

Quantity of Hb (from book)
• Males average 15 g of Hb per 100 ml of blood
• Women average 14 g Hb per 100 ml of blood
**Normally use 20 ml of O2/100 ml of blood for arterial blood

Another Way to Look at Hb Conc.
• Each RBC contains 250 M Hb molecules
• Each Hb molecule contains 4 binding sites
for O2
• So each RBC can carry 1 Billion molecules of O2

So blood circulation carries 25 Sextillion molecules of O2:

Answer 3

know

Question 4

Oxygen-Hemoglobin Saturation Curve
• Under testing conditions at sea-level, Hb is ___% saturated with O2 molecules.
• At elevation (5,000 ft. or higher), % saturation is lower because the pressure gradient between atmospheric pressure and pulmonary pressure is ______ so it is more difficult for O2 to come into the lungs. The
acclimation to this is to produce more RBCs so blood becomes more viscous.

Answer 4

98%

reduced

Question 5

Sites of RBC Production

• Early weeks of embryonic life— primitive, nucleated RBCs are produced in the _____ ______.
• Middle trimester of gestation— main site is the liver but some in the spleen and lymph nodes.
• Last month of gestation and after birth—exclusively produced in bone marrow.
• After age___, stop production in tibia and femur but continues in the marrow of membranous bones
of ribs, sternum, vertebrae and iliac.
• With age, bone marrow becomes less productive.

Answer 5

yolk sac

20

Question 6

Genesis of Blood Cells
• Pluripotential Hematopoietic Stem Cells—these are the stem cells from which ALL types of blood cells are derived.
• Reproduction of the different stem cells are controlled by proteins called _____ ______ (example interleukin-3).
Growth inducers do not cause differentiation, there are another set of proteins called ____________ inducers.
• The intermediate-stage cells that are committed to becoming a specific type of cell are called committed stem cells or ___________ cells.

Answer 6

growth inducers

differentiation

progenitor

Question 7

Stages of Differentiation of RBCs

1. Proerythroblasts
2. First generation cells are called _______Erythroblasts.
3. After these intermediate stages, the cells become ________. At this stage, they pass from the bone marrow into the circulating blood by diapedesis (squeezing through the pores of the capillary membrane).
4. Within 1 to 2 days, the basophilic remnants disappear and the reticulocytes becomes mature erythrocytes (RBCs)

Answer 7

Basophil

Reticulocytes

Question 8

Regulation of RBC Production

• The hormone, erythropoietin, is mainly produced in the _________ (a small amount in the liver).
• Erythropoietin (EPO) is secreted from the kidneys and sent to the bone marrow to produce RBCs thus maintaining homeostatic levels of RBCs.
• Any condition that results in a ________in the O2 delivery to renal tissues increases hypoxia-inducible factor-1 (HIF-1) which stimulates the synthesis and release of EPO.

Answer 8

kidneys

decrease

Question 9

Maturation FAILURE of RBCs X 5
1 • Two vitamins, _____ & _______, are necessary for RBCs to mature properly.
2 • Both vitamins are necessary to form thymidine triphospate which is a building block of ____. Low levels of these vitamins causes low levels of DNA and erythroblastic cells in the kidneys must have DNA for the nucleus to cause cell proliferation (these cells divide rapidly to form new RBCs).
3 • If vitamin B12 and folic acid levels are LOW, the RBCs that are made are larger than normal (called ________) and have flimsy membranes that are irregular in shape and not the normal biconcave appearance.
4 • These abnormally shaped RBCs are capable of carrying O2 but the membranes are more fragile and rupture quite easily—life span is half the term of a normal RBC.
5 • Therefore, deficiency of either vitamin B12 or folic acid results in maturation failure in the process of erythropoiesis.

Answer 9

vitamin B12 and folic acid (folate)

DNA

macrocytes

Question 10

CAUSES of Maturation Failure

1 • Primary cause is the failure of vitamin B12 and folic acid to be absorbed from the gastrointestinal (GI) tract into circulating blood to be delivered to the bone marrow and other tissues.
2 • _______ ________is a blood disorder that causes vitamin B12 deficiency. In this disease the GI mucosa does not secrete a glycoprotein called intrinsic factor. Intrinsic factor is necessary to bind to vitamin B12 so that B12 is available to be absorbed by the gut. By binding with intrinsic factor, vitamin B12 is protected from ___________
3 • Once absorbed, it is stored in large quantities in the ______ and slowly released to the bone marrow. Storage of B12 is often 1000 times the daily required amount so when pernicious anemia starts, it sometime takes 3 to 4 years before diminished B12 absorption is detected.

Answer 10

Pernicious anemia

digestion. **I.F.—THE “BODYGUARD” OF B12

liver

Question 11

Life Span of RBCs

• RBCs normally circulate for about 120 days before being destroyed.
• Mature RBCs do not have a nucleus so they cannot create new RBCs through cell division. They do contain enzymes that help maintain the cell membrane, maintain Hb, and prevent oxidation of other cell proteins.
• With time, these enzymes become less active and the RBCs age and the cell membrane becomes more fragile.
• When the cell membrane becomes fragile, it easily ruptures as it passes through tight spaces such as through the cords of red pulp in the______. A normal RBC is ~8 μm in diameter and must pass through a 3 μm wide space in the red pulp.

Answer 11

spleen

Question 12

Formation of Hb

Formation of Hb begins in the proerythroblast stage and goes through the end of the reticulocyte stage until they become mature erythrocytes.
1• An iron molecule, called a heme unit, and a long polypeptide, called globin, form a sub-unit of Hb called a hemoglobin chain.
2• Four hemoglobin chains bind together and form one whole Hb molecule.
3• There are variations in the chains depending on the amino acid composition of the polypeptide—variations include alpha chains, beta chains, gamma chains, and delta chains.
4• The most common form of Hb molecule is a combination of two alpha chains and two beta chains—this is called______________
5• Since there is one heme unit per chain and there are four chains, each Hb molecule can bind four O2 molecules.
6• Abnormalities in hemoglobin chains can alter the physical characteristic of the Hb molecule and thus its affinity for binding O2.
7• In sickle cell anemia, present in 1% of West Africans and American blacks, Hb is ___________ which contain faulty beta chains. In low O2 concentrations, these Hb molecules form long crystals inside the RBC making it an elongated (sickle) RBC rather than the biconcave shape. This sickle shape makes the RBC membrane more fragile and easily ruptures leading to severe anemia within a few hours (can become life-threatening very quickly).

Answer 12

hemogloboin A.

hemoglobin S

Question 13

Importance of Iron (Fe2+)
• As soon as iron is absorbed from the small intestine, it binds with a beta globulin to from the protein _________ which is transported in circulation via the blood plasma. In this form, it can be released to any tissue in the body that needs it.
• Excess iron is stored primarily in the liver and a smaller amount in the bone marrow. It is stored in the form of ___________ which is called “storage iron”.
• If iron is needed to make new RBCs, it is easily released as transferrin and travels in the blood plasma. People with chronically low levels of circulating transferrin have ___________anemia which results in fewer Hb molecules in the RBCs thus they cannot carry adequate O2.
• The total amount of iron in the body is about 4 to 5 grams.
– 65% in the form of Hb
– 4% in the form of myoglobin
– 1% used for other heme compounds necessary for cellular oxidation
– 0.1 % bound to the protein transferrin found in blood plasma
– ~ 30% stored as ferritin in the liver for later use

Answer 13

transferrin

ferritin

hypochromic

Question 14

Destruction of Hb

• When RBCs burst, Hb is released and immediately surrounded by _________ in many parts of the body but especially the
(1) _________ cells in the liver and macrophages in the
(2) spleen and
(3) bone marrow.
• Within a few days, the macrophages have dismantled the Hb molecules and release the iron into the blood and is carried by transferrin either to the
(1) bone marrow for making Hb for new RBCs or to the (2) liver for storage in the form of ferritin. Most of it goes to storage in the liver.

Answer 14

macrophages

Kupffer

Question 15

4 Types of Anemia

1. _______/_________ anemia—usually
   results from chronic blood loss so iron cannot be
   absorbed fast enough to form Hb and RBCs are
   much SMALLER than normal.
2. ___________ anemia—low vitamin B12 from low
   intrinsic factor not only leads to pernicious anemia
   but the slow production of RBCs results in LARGER
   than normal RBCs. These rupture easily leading
   to anemia.
3. ______ ______ anemia—faulty BETA chains crystallize
   resulting in the sickle shape. Again, the odd shape
   cell ruptures easily.
4. _______ _________—results from
   incompatible Rh factors between mother and
   fetus. The RBCs of the FETUS are fragile and
   rupture easily. Because of this, early blast cells
   are released an are not functional as RBCs. The
   child is born with severe anemia.

Answer 15

MICROcytic, hypochromic

MEGAloblastic

Sickle cell

Erythroblastosis fetalis

Question 16

Effects of Anemia on Circulatory System

Blood viscosity is reduced by half (from 3 times the thickness of water to 1.5
times).
1 • With a decrease in blood viscosity, the resistance to flow is reduced so more blood is returned to the heart which results in increased CO.
2 • Although blood flows more easily, it does NOT have the O2 carrying capacity so tissue_________ becomes a problem. Therefore, the blood vessels to peripheral
tissues vasodilate in response to the O2 demand which further increases CO three to fourfold.
3 • Therefore, the major effects of anemia are greatly increased ____ which results in an increase in pumping workload of the heart.
4 • The increase in CO offsets the reduction in O2 carrying capacity of the blood.
5 • This may work for resting conditions but when a person exercises, the high quantities of blood being pumped from the heart to try to compensate for the
higher tissue hypoxia could result in acute cardiac failure.

Answer 16

hypoxia

CO

Question 17

Polycythemia

• __________ polycythemia is a condition caused by ANOTHER problem such as being at high altitudes or from cardiac failure (which causes low O2 delivery to the tissues). In this case, the bone marrow begins producing large quantities of RBCs.
• A type of secondary polycythemia is called ________ polycythemia and occurs in natives who live at altitudes of 14,000 to 17,000 feet. Instead of the normal 5M RBCs/ μl of blood, they have 6M to 7M RBCs/μl. This allows the natives (such as Sherpas in the Himalayas) to perform tasks in low O2 air.
• _________ __________—this is a pathological condition in which RBC count is as high as 7M to 8M/μl of blood. Instead of a hematocrit of 45%, Hct. is as high as 60 to 70%. Also total blood volume can double which increases viscosity to more than 3 times normal—ten times the thickness of water. This is a genetic condition in which blast cells continue to make new RBCs instead of turning off when enough RBCs are circulating.

Answer 17

Secondary

physiologic

Polycythemia Vera (Erythremia)

Question 18

Effect of Polycythemia on Circulatory Function

• Because of significant increase in blood viscosity, blood flow to the periphery is ________ (increase in resistance to flow).
• Normally, this would decrease VR but because there is more blood with polycythemia, there is about the same amount returning as normal so CO is about normal as well.
• The significant increase in blood viscosity makes it more difficult for the heart to pump the thicker blood so the workload on the heart is __________

Answer 18

sluggish

increased

Question 19

Our bodies have a system for combating these various infectious and toxic agents. This system
works in two ways:
1. Destroying them by means of __________
2. Forming _______to destroy or inactivate the invader.

Answer 19

phagocytosis.

antibodies

Question 20

Leukocytes (White Blood Cells)

• WBCs are produced in the _____ _____ (granulocytes, monocytes, megakaryocytes) and in the lymph tissues (lymphocytes and plasma cells).
• Like RBCs, WBCs are derived from pluripotential hematopoietic stem cells that differentiate and become committed progenitor cells for the various types of WBCs.
• After formation of the WBCs, they are transported via the blood to the different areas of the body where they are needed—areas of inflammation and infections.

Answer 20

bone marrow

Question 21

Types of WBCs include:

• The human body has about _______ WBCs/ μl of blood (as compared to 5M RBCs).

The percent concentration of the different type of WBCs is as follows: 
 Concentration 
1. \_\_\_\_\_\_\_\_\_\_\_ ~ 65% 
 a. Neutrophils (62.0%) 
 b. Eosinophils ( 2.3%) 
 c. Basophils ( 0.4%) 
2. Monocytes ~ 5.0% 
3. \_\_\_\_\_\_\_\_\_~ 30.0% 
4. Megakaryocytes (Thrombocytes) 300,000/ μl of blood

Answer 21

7000

Granulocytes

Lymphocytes

Question 22

Storage and Life Span of WBCs

1. __________ released from storage have a 4 to 8 hour circulating time and another 4 to 5 days in the tissues where they were needed. In severely infected areas, this life span is shortened to hours because the granulocytes work rapidly to destroy the infection and in the process are themselves destroyed.
2. Monocytes– can circulate for 10 to 20 hours and once they enter a tissue they swell in size and can live in the tissue for months unless destroyed doing their function of phagocytosis—these become the tissue named ____________
3. __________ AKA (platelets) are replaced about every 10 days.
4. Lymphocytes– enter the circulatory system with the drainage of lymph from the lymph nodes. They can be re-cycled between the lymph and blood circulations for weeks to months depending on the body’s need for these defense cells.

Answer 22

Granulocytes

marcophages.

Thrombocytes

Question 23

4 Defenses Against Infections

1. WBCs are attracted to inflamed areas by
   chemotaxis.
2. When a tissue becomes inflamed, a dozen different
   types of chemicals draw the WBCs toward it—this is
   chemotaxis.
3. Because no tissue is no more than 50 μm from a
   capillary, the chemotaxic response can bring “hordes”
   of WBCs from the __________ to the inflamed area.
4. Also, the process of ___________ which is how the WBCs leave the capillary pores and go into the tissue spaces. The cell has to go through a portion at a time to fit through the small membrane pores.

Answer 23

capillaries

diapedesis

Question 24

Neutrophils and monocytes are the primary cells that are the first line of attack against invading bacteria, viruses, or other foreign substances.

• _________ are MATURE cells and can destroy bacteria even while circulating in the blood.
• _________ are still IMMATURE cells while in the blood and don’t have the ability to fight infections until they enter the tissue and begin to swell (sometimes increasing diameter by fivefold). These cells are now tissue macrophages and are now capable of attacking and destroying disease agents.

Answer 24

Neutrophils

Monocytes

Question 25

Phagocytes must be selective in what they take in and ingest otherwise normal cells and cell structures would be destroyed.
Phagocytosis has three criteria:
1. Most normal cells and structures have _______ surfaces which resist phagocytosis.
2. Most normal cells and structures have protective _______ coats that repel phagocytes.
3. The immune system develops _______ against foreign substances so if bacteria or viruses enter, they are more susceptible to phagocytosis

Answer 25

smooth

protein

antibodies

Question 26

The process of phagocytosis begins with the molecules on the outer membrane of the invading agent attach to receptors on the phagocyte—this selection and CODING process is called ___________.

1. When a neutrophil attaches to a foreign particle, it encloses the particle and brings it inside the cytoplasm forming a free-floating phagocytic vesicle called a _______________
2. _______ fuse to the phagosome and release proteolytic enzymes that will digest and destroy the enclosed foreign substance. A neutrophil can only destroy up to 20 bacteria before is becomes inactivated and dies. (life span of 4 to 5 days in tissues)

***Macrophages are much larger than
neutrophils so can destroy up to 100 bacteria before they become inactive and die. Also, macrophages are larger so can engulf larger foreign particles. (life span of MONTHS as tissue macrophages inside tissues)

Answer 26

opsonization

phagasome.

Lysosomes

Question 27

Special Types of Macrophages:

1. ___________—once bacteria enter a tissue they cannot enter the blood. If bacteria is not destroyed in the local tissue, they enter the lymph and flow to the lymph nodes (located intermittently along the lymphatic pathway).
2. ___________—these cells are needed because bacteria can enter the body through the GI tract from the food we eat. These bacteria enter the portal blood leaving the GI tract and enter the liver before this
   blood enters general blood circulation.
3. Macrophages in the Spleen—if bacteria succeed in entering general blood circulation, the spleen also has a
   meshwork for bacteria to become trapped. The pores in the capillaries of the spleen are larger so blood can pass through the capillaries and into cords of red pulp.
   The red pulp and venous sinuses are both lined with ______________.

☻☻☻This is the primary site for
phagocytosis of abnormal or old RBCs.

Answer 27

Lymph Nodes

Kupffer Cells in the Liver

macrophages

Question 28

Eosinophils

These granulocytes are produced in high numbers in people with_______ infections. Parasites are often too big to be phagocytized so eosinophils attach to surface molecules on the parasites and release enzymes that will
destroy the parasites.

Answer 28

parasitic

Question 29

Basophils

1. Basophils circulate in the blood and work with mast cells to release ________ into the blood to prevent blood coagulation under normal conditions.
2. Basophils also work with mast cells to release ____________, bradykinin and serotonin during inflammation and during allergic reactions.

Answer 29

heparin

histamines

Question 30

Leukopenia– This condition results from the bone marrow producing a very low number of WBCs. This leaves the body unprotected from many types of bacteria and other foreign substances.

• Under normal conditions, we live in symbiosis with some level of bacteria in almost all mucous lined organs (mouth, GI tract, lungs, etc.). However, when the bone marrow stops producing WBCs, the bacteria take over very quickly. Within 2 days of the bone marrow not producing WBCs,_______ begin to form in the mucous areas and the person might develop a deadly respiratory infection. Without treatment, death from acute leukopenia can occur within a week.

Answer 30

ulcers

KNOW THAT:
***Radiation, chemotherapy, exposure to some strong antibiotics can destroy the bone marrow’s ability to produce WBCs. A patient must be given blood transfusions, antibiotics and other drugs to ward off massive infection until new bone marrow develops and become capable of producing blood cells. This can take weeks to months.

Question 31

Leukemia— This is an uncontrolled production of WBCs and is a cancerous mutation of myelocytes and lymphocytes.

1. Leukemia of the myelocytes usually begins in the ____ ______ and then spreads to other areas of the body so that abnormal WBCs are rapidly produced in the spleen, lymph nodes and liver as well.
2. Leukemia of lymphocytes usually begins in the ____ ______ and spreads to other areas of the body such as the spleen and liver.
3. Although some myelocyte leukemia cells partially differentiate, they do not result in mature WBCs. Most often, they are not identifiable as a granulocyte and the more _____________ the more ACUTE the leukemia.
   ACUTE forms of leukemia can lead to death within a few months if not treated.

CHRONIC forms of leukemia may take 10 to 20 years to develop.

Answer 31

bone marrow

lymph nodes

undifferentiated,

Question 32

Effects of Leukemia on the Body

1. Leukemia originating in the bone marrow may invade the bone itself causing ____________and the bones become __________ and can fracture easily.
2. Almost all leukemias eventually invade the spleen,lymph nodes and liver regardless of origin of the disease. As a result, the person develops severe ________, tendency for bleeding because of a lack of platelets (thrombocytopenia), and tendency for infections.
3. Often, the leukemic tissues reproduce cells so quickly that they use the metabolic substrates, especially amino acids. As a result, the person is fatigued and other tissues start to deteriorate because of the use of amino
   acids for reproducing leukemic cells. Therefore, while the leukemia tissues grow, the other body tissues are ____________.

Answer 32

PAIN

fragile

anemia

weakened