Circulatory System

-Blood
Al-Farabi Kazakh
National
University
Higher School of
Medicine
◆ PART I
 LEARNING OUTCOMES

As a result of the lesson you will be able to:

❏ Describe the functions and major components of the

circulatory system;

❏ Describe the components and physical properties of blood;

❏ Describe the composition of blood plasma;

❏ Explain the significance of blood viscosity and osmolarity;

❏ describe in general terms how blood is produced

Al-Farabi Kazakh National University

Higher School of Medicine
 LEARNING OUTCOMES

As a result of the lesson you will be able to:

❏ Explain what determines a person’s ABO and Rh

blood types and how this relates to transfusion
compatibility;

❏ list some blood groups other than ABO and Rh and

explain how they may be useful;

❏ describe the effects of a blood type incompatibility

between mother and fetus.

Al-Farabi Kazakh National University

Higher School of Medicine
 Circulatory System
• circulatory system consists
of the heart, blood vessels
and blood
• cardiovascular[cardio = heart;
vas = vessel] system refers
only to the heart and blood
vessels
• hematology[hem, hemato =
blood; logy = study of ] – the
study of blood

5
© Gerard Vandystadt/Photo Researchers, Inc.
Circulatory System
• functions of circulatory
system

– transport
• O2, CO2, nutrients, wastes,
hormones, and stem cells
– protection
• inflammation, limit spread of
infection, destroy
microorganisms and cancer
cells, neutralize toxins, and
initiates clotting
– regulation
• fluid balance, stabilizes pH of
ECF, and temperature control

6
© Gerard Vandystadt/Photo Researchers, Inc.
Identify at least two each of the transport, protective, and regulatory
functions of the circulatory system

why an excessive loss of blood is quickly fatal

7
Components and General Properties of
Blood
• adults have 4-6 L of blood
• a liquid connective tissue consisting of
cells and extracellular matrix
– plasma – matrix of blood
• a clear, light yellow fluid
– formed elements - blood cells and cell
fragments
• red blood cells, white blood cells, and platelets

8
Components and General Properties of
Blood
• seven kinds of formed elements
– erythrocytes [erythro = red; cyte = cell ] - red blood cells
(RBCs)
– platelets
• cell fragments from special cell in bone marrow
– leukocytes[leuko = white; cyte = cell ] - white blood cells
(WBCs)
• five leukocyte types divided into two categories:
• granulocytes [with granules]
– neutrophils
– eosinophils
– basophils
• agranulocytes [without granules]
– lymphocytes
– monocytes
9
Formed Elements of Blood
What do erythrocytes and platelets lack that the other formed elements have?

Monocyte
Small
lymphocyte
Neutrophil
Platelets

Eosinophil
Small Erythrocyte
lymphocyte

Young (band)
neutrophil
Neutrophil

Monocyte

Large
lymphocyte
Neutrophil
Basophil

10
Separating Plasma From Formed Elements of Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Withdraw
blood • hematocrit - centrifuge
blood to separate
components
– erythrocytes are heaviest and
settle first
Centrifuge
• 37% to 52% total volume
– white blood cells and
Plasma platelets
(55% of whole blood) • 1% total volume
• buffy coat
Buffy coat: leukocytes
– plasma
and platelets • the remainder of volume
(<1% of whole blood)
• 47% - 63%
Erythrocytes Formed • complex mixture of water, proteins,
(45% of whole blood) elements
nutrients, electrolytes, nitrogenous
wastes, hormones, and gases

11
Figure 18.2
▶▶▶APPLY WHAT YOU KNOW

Based on your body weight, estimate the volume (in liters) and weight (in kilograms) of

your own blood

 Plasma and Plasma Proteins
▶ ▶ ▶ APPLY WHAT YOU KNOW
How could a disease such as liver cancer or hepatitis result in impaired blood clotting ?

• plasma – liquid portion of blood

– serum – remaining fluid when blood clots and the solids are
removed
• identical to plasma except for the absence of fibrinogen

• 3 major categories of plasma proteins

– albumins – smallest and most abundant
• contributes to viscosity and osmolarity, influences blood pressure,
flow and fluid balance
– globulins (antibodies)
• provide immune system functions
• alpha, beta and gamma globulins
– fibrinogen
• precursor of fibrin threads that help form blood clots

• plasma proteins formed by liver

– except gamma globulins (produced by plasma cells) 13
Nonprotein Components of Plasma
• nitrogenous compounds
– free amino acids
• from dietary protein or tissue breakdown
– nitrogenous wastes (urea)
• toxic end products of catabolism
• normally removed by the kidneys

• nutrients
– glucose, vitamins, fats, cholesterol, phospholipids, and
minerals
• dissolved O2, CO2, and nitrogen

• electrolytes
– Na+ makes up 90% of plasma cations
14
 Properties of Blood
• viscosity - resistance of a fluid to flow, resulting
from the cohesion of its particles
– whole blood 4.5 - 5.5 times as viscous as water
– plasma is 2.0 times as viscous as water
• important in circulatory function

• osmolarity of blood - the total molarity of those

dissolved particles that cannot pass through the
blood vessel wall
– if too high, blood absorbs too much water, increasing the
blood pressure
– if too low, too much water stays in tissue, blood pressure
drops and edema occurs
– optimum osmolarity is achieved by bodies regulation of
sodium ions, proteins, and red blood cells.
15
Starvation and Plasma Proteins
• hypoproteinemia
– deficiency of plasma proteins
• extreme starvation
• liver or kidney disease
• severe burns

• kwashiorkor
– children with severe protein deficiency
• fed on cereals once weaned
– thin arms and legs
– swollen abdomen

16
Several conditions can lead
to hypoproteinemia, a
deficiency of plasma protein:
extreme starvation or dietary
protein deficiency, liver
diseases that interfere with
protein synthesis, and
protein loss through the
urine or body surface in the
As the protein content of the blood plasma drops, so does its
osmolarity. The bloodstream loses more fluid to the tissues than it
reabsorbs by osmosis. Thus, the tissues become edematous and a
pool of fluid may accumulate in the abdominal cavity—a condition
called ascites (ah-SY-teez).
Children who suffer severe dietary protein deficiencies often
exhibit a condition called kwashiorkor (KWASH-ee-OR-cor) (fig.
18.3). The arms and legs are emaciated for lack of muscle, the skin
is shiny and tight with edema, and the abdomen is swollen by
ascites. Kwashiorkor is an African word for a “deposed” or
“displaced” child who is no longer breast-fed. Symptoms appear
when a child is weaned and placed on a diet consisting mainly of
rice or other cereals. Children with kwashiorkor often die of
diarrhea and dehydration.
What does hemopoiesis mean? After birth, what one
cell type is the starting point for all hemopoiesis

20
 Hemopoiesis
• Adult production of 400 billion platelets, 200 billion RBCs and
10 billion WBCs every day
• hemopoiesis[hemo = blood; poiesis = formation ] – the
production of blood, especially its formed elements
• hemopoietic tissues produce blood cells
– yolk sac produces stem cells for first blood cells
• colonize fetal bone marrow, liver, spleen and thymus
– liver stops producing blood cells at birth
– spleen remains involved with lymphocyte production
– red bone marrow produces all seven formed elements
• pluripotent stem cells (PPSC)
– formerly called hemocytoblasts or hemopoietic stem cells
• colony forming units – specialized stem cells only producing one class
of formed element of blood
• myeloid [bone marrow ] hemopoiesis – blood formation in the bone
marrow
• lymphoid hemopoiesis – blood formation in the lymphatic organs
21
Charles Drew was a scientist who lived
and died in the grip of irony. After
receiving his M.D. from McGill
University of Montreal in 1933, Drew
became the first black person to pursue
the advanced degree of Doctor of
Science in Medicine, for which he
studied transfusion and blood banking
at Columbia University. He became the
director of a new blood bank at
Drew saved countless lives by
convincing physicians to use plasma
rather than whole blood for battlefield
and other emergency transfusions.
Whole blood could be stored for only a
week and given only to recipients with
compatible blood types. Plasma could
be stored longer and was less likely to
cause transfusion reactions.
When the U.S. War Department issued a directive forbidding the storage of
Caucasian and Negro blood in the same military blood banks, Drew denounced
the order and resigned his position. He became a professor of surgery at Howard
University in Washington, D.C., and later chief of staff at Freedmen’s Hospital.
He was a mentor for numerous young black physicians and campaigned to get
them accepted into the medical community. The American Medical Association,
however, refused to admit black members until the 1960s, excluding even Drew
himself.
Late one night in 1950, Drew and three colleagues set out to volunteer their medical
services to an annual free clinic in Tuskegee, Alabama. Drew fell asleep at the wheel
and was critically injured in the resulting accident. Contrary to a myth that Drew was
refused emergency treatment because of his race, doctors at the nearest hospital
administered blood and attempted to revive him. Yet, for all the lives he saved
through his pioneering work in transfusion, Drew himself bled to death at the age of
45.
 Blood Types
• Blood types and transfusion compatibility are a matter of
interactions between plasma proteins and erythrocytes

• Karl Landsteiner discovered blood types A, B and O in

1900
– won Nobel Prize

• Blood types are based on interactions between antigens

and antibodies

26
Blood Antigens and Antibodies
• antigens
– complex molecules on surface of cell membrane that are unique
to the individual
• used to distinguish self from foreign
• foreign antigens generate an immune response
• agglutinogens – antigens on the surface of the RBC that is the
basis for blood typing
• antibodies
– proteins (gamma globulins) secreted by plasma cells
• part of immune response to foreign matter
• bind to antigens and mark them for destruction
• forms antigen-antibody complexes
• agglutinins – antibodies in the plasma that bring about transfusion
mismatch
• agglutination
– antibody molecule binding to antigens
– causes clumping of red blood cells

27
 Blood Types
• RBC antigens called Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Type O Type B

agglutinogens
– called antigen A and B leaves

– determined by
carbohydrate moieties Type A Type AB

found on RBC surface

• antibodies called
agglutinins Key
Galactose

– found in plasma Fucose

– anti-A and anti-B N-acetylgalactosamine

Figure 18.12 28
What Scientists have developed a method of enzymatically
splitting N-acetylgalactosamine off the glycolipid of type A
blood cells . What potential benefit do you think they saw
as justifying their research effort?

29
 ABO Group
• your ABO blood type is determined by presence or
absence of antigens (agglutinogens) on RBCs
– blood type A person has A antigens
– blood type B person has B antigens
– blood type AB has both A and B antigens
– blood type O person has neither antigen
• most common - type O
• rarest - type AB

30
 Plasma Antibodies
• antibodies (agglutinins); anti-A and anti-B
• appear 2-8 months after birth; at maximum concentration
at 10 yr.
– antibody-A and/or antibody-B (both or none) are found in plasma
• you do not form antibodies against your antigens

• agglutination
– each antibody can attach to several foreign antigens on several
different RBCs at the same time
• responsible for mismatched transfusion reaction
– agglutinated RBCs block small blood vessels, hemolyze, and
release their hemoglobin over the next few hours or days
– Hb blocks kidney tubules and causes acute renal failure

31
ABO Blood Typing
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Type A

Type B

Type AB

Figure 18.14
Type O
32
© Claude Revey/Phototake
Agglutination of Erythrocytes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Antibodies
(agglutinins)

Figure 18.13
33
Transfusion Reaction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Blood from
type A donor leaves

Type B
(anti-A)
recipient
Donor RBCs
agglutinated by
recipient plasma
Agglutinated RBCs
block small vessels
34
Figure 18.15
Universal Donors and Recipients
• universal donor
– Type O – most common blood type
– lacks RBC antigens
– donor’s plasma may have both antibodies
against recipient’s RBCs (anti-A and anti-B)
• may give packed cells (minimal plasma)

• universal recipient
– Type AB – rarest blood type
– lacks plasma antibodies; no anti- A or B

35
 Rh Group
• Rh (C,D,E) agglutinogens discovered in
rhesus monkey in 1940
– Rh D is the most reactive and a patient is
considered blood type Rh+ if they have D
antigen (agglutinogens) on RBCs
– Rh frequencies vary among ethnic groups
• Anti-D agglutinins not normally present
– form in Rh- individuals exposed to Rh+ blood
• Rh- woman with an Rh+ fetus or transfusion of Rh+
blood
• no problems with first transfusion or pregnancy
36
Hemolytic Disease of Newborn
• occurs if Rh- mother has formed
antibodies and is pregnant with second
Rh+ child
– Anti-D antibodies can cross placenta

• prevention
– RhoGAM given to pregnant Rh- women
• binds fetal agglutinogens in her blood so she will
not form Anti-D antibodies

37
Hemolytic Disease of Newborn
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

leaves

Rh- mother

Rh
antigen
Second
Rh+ fetus Rh+ fetus

Uterus
Anti-D
Amniotic sac antibody
and chorion

Placenta

(a) First pregnancy (b) Between pregnancies (c) Second pregnancy

• Rh antibodies attack fetal blood

causing severe anemia and toxic brain syndrome 38
A baby with HDN typically has jaundice and an
enlarged spleen. Explain these effects.

39
In hemolytic disease of the newborn, RBCs break down and
release hemoglobin, and the hemoglobin is degraded to
bilirubin at such a fast rate that the liver cannot dispose of
the bilirubin. It accumulates in the blood and produces
jaundice. Splenomegaly, enlargement of the spleen, occurs
because the spleen is one of the sites of the accelerated
erythropoiesis that occurs in HDN.

40
A bone marrow transplant is one treatment option for leukemia, sickle-
cell disease, some forms of anemia, and other disorders. The principle is
to replace cancerous or otherwise defective marrow with donor stem cells
in hopes that they will rebuild a population of normal marrow and blood
cells. The patient is first given chemotherapy or radiation to destroy the
defective marrow and eliminate immune cells (T cells) that would attack
the donated marrow. Bone marrow is drawn from the donor’s sternum or
hip bone and injected into the recipient’s circulatory system. Donor stem
cells colonize the patient’s marrow cavities and, ideally, build healthy
marrow.
There are, however, several drawbacks to bone marrow transplant. For
one, it is difficult to find compatible donors. Surviving T cells in the
patient may attack the donor marrow, and donor T cells may attack the
patient’s tissues (the graft-versus-host response). To inhibit graft
rejection, the patient must take immunosuppressant drugs for life. These
drugs leave a person vulnerable to infection and have many other adverse
side effects. Infections are sometimes contracted from the donated
marrow itself. In short, marrow transplant is a high-risk procedure; up to
one-third of patients die from complications of treatment.
An alternative with several advantages is to use blood from placentas,
which are normally discarded at every childbirth. Placental blood
contains more stem cells than adult bone marrow, and is less likely to carry
infectious microbes. With the parents’ consent, it can be harvested from
the umbilical cord with a syringe and stored almost indefinitely, frozen in
liquid nitrogen at cord blood banks. The immature immune cells in cord
blood have less tendency to attack the recipient’s tissues; thus, cord blood
transplants have lower rejection rates and do not require as close a match
between donor and recipient, meaning that more donors are available to
patients in need. Pioneered in the 1980s, cord blood transplants have
successfully treated leukemia and a wide range of other blood diseases.
Efforts are being made to further improve the procedure by stimulating
fetal stem cells to multiply before the transplant, and by removing fetal T
cells that may react against the recipient.
◆ PART II
 LEARNING OUTCOMES

As a result of the lesson you will be able to:

❏Discuss the structure of erythrocytes (RBCs)

❏Describe the structure of hemoglobin

❏Discuss the structure of leukocytes

Al-Farabi Kazakh National University

Learning outcomes:
As a result of the lesson you will be able to:

 Microscopic and ultramicroscopic structure of erythrocytes, leucocytes, and

thrombocytes.
 Embryonal development of blood
 Blood plasma, its functional significance
 Erythrocytes
 Classification of leukocytes
 Granulocytes
 Agranulocytes
 Blood platelets
 photomicrographs and diagrams of the cells of blood
Source Undetermined
Source Undetermined
Major Plasma Proteins

Protein Function
Albumin Maintain colloid osmotic pressure;
transport insoluble metabolites
Globulins
 and  Transport metal ions, protein-bound
lipids, lipid-soluble vitamins

 Antibodies for host defense

Complement proteins Destruction of microorganisms

Clotting factors Formation of blood clots

Plasma lipoproteins Transport of triglycerides and

cholesterol to/from liver
Cells of the blood

● Erythrocytes (red blood cells, RBC)

● Platelets (thrombocytes)
● Leukocytes (white blood cells, WBC)
○ Granulocytes (with specific granules)
■ Neutrophil (~60% of WBC)
■ Eosinophil (~4% of WBC)
■ Basophil (<1% of WBC)
○ Agranulocytes (without specific granules)
■ Lymphocyte (B-cell, T-cell) (~27% of WBC)
■ Monocyte (~8% of WBC)
 FYI, blood smear procedure

● The procedure for making a blood smear

is shown at left.
● After the smear is made, it is air-dried
Image of blood
smear procedure and then stained. Common stains are
removed Wright's stain and Giemsa stain. The
stains generally include two or more
dyes, one of them a basic dye (often
methylene blue) and another an acidic
dye (usually eosin). Reddish-blue
azures are formed when methylene blue
Original Source: Junqueira's is oxidized (metachromasia). Cells
histology text, 6th ed., page 231.
usually stain pink/red with acidic dye and
BloodSmear-23J91(2).tif.
nuclei stain purple/black with basic dye,
while specific granules stain
characteristically.
● Remember that the cells you see in a
blood smear have not been sectioned.
Instead you are seeing whole cells dried
down on the glass.
Human blood smear, with RBCs, WBCs and platelets

Platelets

RBC
Lymphocyte

Neutrophil

Dr. A. Kent Christensen

Erythrocyte (red blood cell, RBC)

1. Life span in blood: About 120 days.

2. Size and shape:
○ biconcave disk, 8 µm diameter, 2m at thickest point, 1 m at
thinnest
○ shape maintained by a cytoskeletal complex inside the plasma
membrane (involving spectrin, actin and other components)
○ flexible: RBC’s normally bend to pass through small capillaries
3. LM appearance in smear: Pink circle with light center (center
is thinner because of the biconcave shape). No nucleus.
4. TEM appearance: Solid dark gray cytoplasm, because of
highly concentrated hemoglobin.
5. Function:
○ Transport of oxygen and carbon dioxide
■ bound to hemoglobin (oxyhemoglobin and carboxyhemoglobin)
■ majority of CO2 transported as HCO3-
○ pH homeostasis
■ carbonic anhydrase: CO2 + H2O  HCO3- + H+
■ band 3 membrane protein: exchanges HCO3- for extracellular Cl-
RBCs, scanning electron microscopy

Junqueira's Basic Histology, 10th edition, page 235

Red blood cells in a blood smear

RBC

Platelet

Mizoguti slide collection (J). J-199.

RBC, transmission electron microscopy
RBC

Platelet

Erlandsen's slide set (MH). MH-2G3..

◆ PART II
 LEARNING OUTCOMES

As a result of the lesson you will be able to:

❏ Discuss the structure and function of erythrocytes (RBCs);

❏ Describe the structure and function of hemoglobin;

❏ State and define some clinical measurements of RBC and

hemoglobin quantities;

❏ Describe the life history of erythrocytes; and

❏ Name and describe the types, causes, and effects of RBC excesses
and deficiencies.

Al-Farabi Kazakh National University

Erythrocytes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.

Capillary
wall

Erythrocytes

(c)
Figure
7 µm
© Dr. Don W. Fawcett/Visuals Unlimited
● two principal functions:
18.4c
– carry oxygen from lungs to cell tissues
– pick up carbon dioxide from tissues and bring to lungs
● insufficient RBCs may kill in few minutes due to lack
of oxygen to tissues 5
9
Erythrocytes (RBCs)
●disc-shaped cell with thick rim
– 7.5 mM diameter and 2.0 mm thick
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.
Surfaceview
at rim
– lose nearly all organelles during
development 7.5 µm
■lack mitochondria
– anaerobic fermentation to produce ATP
■lack of nucleus and DNA
– no protein synthesis or mitosis
– blood type determined by surface
glycoprotein and glycolipids 2.0 µm
– cytoskeletal proteins (spectrin
(a) Sectional view
and actin) give membrane
durability and resilience Figure 6
■stretch and bend as squeeze through 0
Why are erythrocytes caved in at the
center?

6
1
Erythrocyte Production (Erythropoiesis)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.
Pluripotent Colony-forming Precursor Mature
stem cell unit (CFU) cells cell

Erythrocyte CFU Erythroblast Reticulocyte Erythrocyte

● 2.5 million RBCs are produced per second Figure 18.6

● average lifespan of about 120 days
● development takes 3-5 days
– reduction in cell size, increase in cell number, synthesis of hemoglobin
and loss of nucleus
● first committed cell - erythrocyte colony forming unit
– has receptors for erythropoietin (EPO) from kidneys
● erythroblasts (normoblast) multiply and synthesize
hemoglobin
● nucleus discarded to form a reticulocyte
– named for fine network of endoplasmic reticulum 6
2
– 0.5 to 1.5% of circulating RBCs are reticulocytes
RBC Form and Function
●gas transport - major function
– increased surface area/volume ratio
■due to loss of organelles during maturation
■increases diffusion rate of substances
– 33% of cytoplasm is hemoglobin (Hb)
■280 million hemoglobin molecules on one RBC
■O2 delivery to tissue and CO2 transport to lungs

– carbonic anhydrase (CAH) in cytoplasm

■produces carbonic acid from CO2 and water
■important role in gas transport and pH balance
6
3
Hemoglobin (Hb) Structure
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.

● each Hb molecule consists of:

– four protein chains – globins Beta Alpha

– four heme groups Heme

groups

(a) Alpha Beta

● heme groups
– nonprotein moiety that binds O2 to
CH3 CH CH2
ferrous ion (Fe2+) at its center C C
HC C C CH

● globins - four protein chains

N C C CH
CH3 C C 3
N Fe2+ N
CH2 C C C CH CH2
– two alpha and two beta chains CH2
C
HC C
N
C CH
COOH
– 5% CO2 in blood is bound to C C
CH2 CH3

globin moiety CH2

COOH
(b)

● adult vs. fetal hemoglobin Figure 18.5

6
4
In what way does this
exemplify a quaternary
protein structure? What is
the prosthetic group of
hemoglobin? ?
Erythrocytes and Hemoglobin
●RBC count and hemoglobin concentration
indicate amount of O2 blood can carry
– hematocrit [hemato = blood; crit = to separate ](packed cell
volume) – percentage of whole blood volume
composed of red blood cells
■men 42- 52% cells; women 37- 48% cells
– hemoglobin concentration of whole blood
■men 13-18g/dL; women 12-16g/dL
– RBC count
■men 4.6-6.2 million/mL; women 4-2-5.4 million/mL
●values are lower in women
– androgens stimulate RBC production
– women have periodic menstrual losses
– hematocrit is inversely proportional to percentage of
body fat 66
Erythrocyte Disorders
●polycythemia[poly = many; cyt = cell; hem = blood; ia = condition ] - an
excess of RBCs
●[The RBC count is normally 4.6 to 6.2 million RBCs/μL in men and 4.2 to 5.4 million/μL in
women.The hematocrit (PCV) In men, it normally ranges between 42% and 52%; in

women, between 37% and 48%. ]

– primary polycythemia (polycythemia vera)
■cancer of erythropoietic cell line in red bone marrow
– RBC count as high as 11 million/mL; hematocrit 80%
– secondary polycythemia
■from dehydration, emphysema, high altitude, or physical
conditioning
– RBC count up to 8 million/mL

●dangers of polycythemia
– increased blood volume, pressure, viscosity
■can lead to embolism, stroke or heart failure 67
▶ ▶ ▶ APPLY WHAT YOU KNOW
Explain why the hemoglobin concentration
could appear deceptively high in a patient
who is dehydrated, when in fact the patient
does not have a hemoglobin or RBC excess?

68
Anemia[an = without; em = blood; ia = condition ]

●causes of anemia fall into three categories:

– inadequate erythropoiesis or hemoglobin
synthesis
■kidney failure and insufficient erythropoietin
■iron-deficiency anemia
■inadequate vitamin B12 from poor nutrition or lack of intrinsic
factor (pernicious anemia)
■hypoplastic anemia – slowing of erythropoiesis
■aplastic anemia - complete cessation of erythropoiesis

– hemorrhagic anemias from bleeding

– hemolytic anemias from RBC destruction
69
Anemia
●anemia has three potential consequences:
– tissue hypoxia and necrosis
■patient is lethargic
■shortness of breath upon exertion
■life threatening necrosis of brain, heart, or kidney

– blood osmolarity is reduced producing tissue

edema
– blood viscosity is low
■heart races and pressure drops
■cardiac failure may ensue 70
 Sickle-Cell Disease
Copyright © The McGraw-Hill Companies, Inc. Permission required for
reproduction or display.
● hereditary hemoglobin defects
that occur mostly among
people of African descent

● caused by a recessive allele

that modifies the structure of
the hemoglobin molecule (HbS)
– differs only on the sixth amino
acid of the beta chain
– HbS does not bind oxygen well
– RBCs become rigid, sticky,
pointed at ends
– clump together and block small
blood vessels causing intense
pain
– can lead to kidney or heart failure,
© Meckes/Ottawa/Photo Researchers, Inc.
7 µm
stroke, rheumatism or paralysis 71
Figure
Case Presentation

Dolores Welborn is a 28-year-old attorney living in Portland, Oregon.

Dolores is in the second trimester of pregnancy with her first child, and
though her pregnancy had been progressing normally, recently she has
noticed that she tires very easily and is short of breath from even the
slightest exertion. She also has experienced periods of light-headedness,
though not to the point of fainting. Other changes she has noticed are
cramping in her legs, a desire to crunch on ice, and the fact that her
tongue is sore. She doubts that all of these symptoms are related to one
another, but she is concerned, and she makes an appointment to see her
physician.

72
Case Presentation

Upon examining Dolores, her physician

finds that she has tachycardia, pale gums
and nail beds, and her tongue is swollen.
Given her history and the findings on her
physical exam, the physician suspects that
Dolores is anemic and orders a sample of
her blood for examination. The results are
shown in Table.

73
Case Presentation

A diagnosis of anemia due to iron deficiency is made and oral iron

supplements prescribed. Dolores’ symptoms are eliminated within a
couple of weeks and the remainder of her pregnancy progresses without
difficulty.

Describe the structure of a molecule of hemoglobin and explain the role

played by iron in the transport of oxygen.

74
Hemoglobin (Hb) Structure
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction
or display.

● each Hb molecule consists of:

– four protein chains – globins Beta Alpha

– four heme groups Heme

groups

(a) Alpha Beta

● heme groups
– nonprotein moiety that binds O2 CH3 CH CH2
C C
to ferrous ion (Fe2+) at its center HC C C CH
N C C CH
CH3 C C
● globins - four protein chains
3
N Fe2+ N
CH2 C
C N C C CH CH2
– two alpha and two beta chains CH2
COOH
HC C C CH

C C
– 5% CO2 in blood is bound to CH2 CH3
CH2

globin moiety (b)

COOH

75
Figure 18.5
How is iron stored and transported in the body?

76
Nutritional Needs for Erythropoiesis
● iron - key nutritional requirement
– lost daily through urine, feces, and bleeding
■men 0.9 mg/day and women 1.7 mg/day
– low absorption rate of iron requires consumption of 5-20
mg/day
■dietary iron: ferric (Fe3+) and ferrous (Fe2+)
– stomach acid converts Fe3+ to absorbable Fe2+
– gastroferritin[gastro = stomach; ferrit = iron; in = protein] binds Fe2+ and
transports it to small intestine
– absorbed into blood and binds to transferrin for transport to bone marrow,
liver, and other tissues
- bone marrow for hemoglobin, muscle for myoglobin, and all cells use for
cytochromes in mitochondria
■liver apoferritin[apo = separated from; ferrit = iron; in = protein] binds to create
ferritin for storage 77
Iron Metabolism
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reproduction or display.

leaves
8 Remaining transferrin is distributed 1 Mixture of Fe2+ and
to other organs where Fe2+ is used Fe3+ is ingested
to make hemoglobin, myoglobin, etc.

7 Fe2+ binds to Fe3+

apoferritin Ferritin 2 Stomach acid
to be stored converts Fe3+
as ferritin Apoferritin Fe2+ to Fe2+
Gastroferritin
6 In liver, some transferrin
releases Fe2+ for storage 3 Fe2+ binds to
Blood plasma gastroferritin
5 In blood plasma, Transferrin 4 Gastroferritin transports
Fe binds to transferrin
2+
Fe2+ to small intestine and
releases it for absorption

Figure 18.7 78
Nutritional Needs for Erythropoiesis

● Vitamin B12 and folic acid

– rapid cell division and DNA synthesis that occurs
in erythropoiesis

● Vitamin C and copper

– cofactors for enzymes synthesizing hemoglobin
■copper is transported in the blood by an alpha
globulin called ceruloplasmin[cerulo = blue-green, the color of
oxidized copper; plasm = blood plasma; in = protein ]

79
 What is Iron Deficiency Anemia (ida) and how frequently does it
occur?

80
What What are the most common causes of ida? Why are women more
prone to ida than men?

81
What are the red blood cell indices, and what tests are diagnostic for
ida? How is ida treated and prevented?

82
Erythrocyte Homeostasis
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display.
Hypoxemia
● negative feedback control (inadequate O2 transport)
Increased
O2 transport
– drop in RBC count causes kidney Sensed by liver and kidneys leaves

hypoxemia [ hyp = below normal;

ox = oxygen; emia = blood
condition ]
Increased
– kidney production of erythropoietin RBC count

stimulates bone marrow

Accelerated
– RBC count increases in 3 - 4 days erythropoiesis
Secretion of
erythropoietin

● stimuli for increasing

erythropoiesis Stimulation of
– low levels O2 (hypoxemia) red bone marrow

– high altitude
– increase in exercise Figure 18.8 83
Erythrocytes Death and Disposal

● RBCs lyse in narrow channels in spleen

● Hemolysis(hemo = blood; lysis = splitting, breakdown ), the rupture of RBCs,
releases hemoglobin and leaves empty plasma membranes
● macrophages in spleen
– digest membrane bits
– separate heme from globin
■ globins hydrolyzed into amino acids
■ iron removed from heme
– heme pigment converted to biliverdin [bili = bile; verd = green; in = substance ]
(green)
– biliverdin converted to bilirubin[bili = bile; rub = red; in = substance ] (yellow)
– released into blood plasma (kidneys - yellow urine)
– liver removes bilirubin and secretes into bile
- concentrated in gall bladder: released into small intestine; bacteria create urobilinogen (brown
84
feces)
Erythrocytes Recycle/Disposal
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display.
Amino Erythropoiesis in
acids red bone marrow
Iron
Folic acid
Nutrient
Vitamin
absorption
B12

Small intestine Erythrocytes

circulate for
120 days

Expired erythrocytes
break up in liver and spleen

Cell fragments
phagocytized

Hemoglobin
degraded
Heme Globin Figure 18.9
Biliverdin Iron Hydrolyzed to free
Bilirubin Storage amino acids
ReuseLoss by
Bile menstruation, 85
injury, etc.
Feces