PHYSIOLOGY

CHAPTER 33: Red Blood Cells, Anemia,

and Polycythemia

OUTLINE o Depends to a minor degree on blood

viscosity
I. Blood o Mostly due to diameter of blood vessels,
a. Definition and General overview particularly the arterioles.
b. Components  Physical Characteristics:
II. Hematopoiesis o Blood constitutes:
a. Definition and General Over view  total volume of extracellular
b. Hematopoiesis Diagram fluid: 20%
III. Red Blood Cell  total body mass: 8%
a. Anatomy and Physiology o Temperature: 38°C
b. Life Cycle o pH: 7.35 to 7.45
c. Erythropoiesis o In the average human body weight,
d. Hemoglobin Formation volume of blood is:
e. Disorders of the RBC  male (70kg): approximately 5.6L
IV. Summary Table and Diagram  female: approximately 4.5L
Difference in volume for each gender is
V. Resources due to the difference of body size.

I. BLOOD

A. DEFINITION AND GENERAL OVERVIEW

 Blood is a liquid connective tissue that consists
of cells (formed elements) surrounded by a
liquid extracellular matrix (plasma).
 Blood has three general functions:
1. Transportation:
Transports oxygen, carbon dioxide,
nutrients, hormones, heat, and wastes.
2. Regulation:
Regulates pH, body temperature,
and water content of cells.
3. Protection:
Protects against blood lost through clotting,
and against disease through phagocytic
white blood cells and proteins such as
antibodies, interferons and complement.
 Manner of flow through the circulation:
Forward motion by:
o by pumping of the Heart
o Diastolic recoil of the walls of arteries
o Compression of veins by skeletal
muscles during exercise
o Negative pressure by the thorax during
inspiration.
Resistance of flow by:
Figure 1: Centrifuged whole blood
B. COMPONENTS
 Formed Elements
all formed in the Red Bone Marrow
o Erythrocytes: Red blood cells (RBCs) transport
oxygen from the lungs to body cells and deliver
carbon dioxide from body cells to the lungs.
o Leukocytes: White Blood (WBCs) protection from
invading pathogens and other foreign substances.
o Platelets: are fragments of cells that do not have
a nucleus. Among other actions, they release
chemicals that promote blood clotting when
blood vessels are damaged.
 Plasma
o Composed of:
91.5% water
8.5% solutes,
7% by weight are proteins.
Albumins: 54%
Globulins: 38%
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CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia

Fibrinogen: 7% Seen in: axial skeleton, pectoral and pelvic girdles,

other solutes: electrolytes, nutrients, and the proximal epiphyses of the humerus and
regulatory substances such as enzymes and femur.
hormones, gases, and waste products such as  pluripotent stem cells or hemocytoblasts: 0.05–
urea, uric acid, creatinine, ammonia and 0.1% of red bone marrow cells
bilirubin. o derived from mesenchyme (tissue from which
 Regulation by Plasma almost all connective tissues develop).
o Hydrostatic Pressure  have the capacity to develop into many
 the pressure that water in blood plasma different types of cells
exerts against blood vessel walls
 Blood Hydrostatic Pressure (BHP):
“pushes” fluid out of capillaries into
interstitial fluid.
 Interstitial fluid hydrostatic pressure
(IFHP):
 opposing pressure of BHP is the
interstitial fluid, called, which
“pushes” fluid from interstitial
spaces back into capillaries.
o Colloid Oncotic Pressure
 Blood colloid osmotic pressure (BCOP):
Figure 2: Hematopoiesis flow chart
 force caused by the colloidal
suspension of large proteins in
III. RED BLOOD CELLS
plasma that averages 26 mmHg in
most capillaries
 effect of BCOP is to “pull” fluid from A. ANATOMY AND PHYSIOLOGY
interstitial spaces into capillaries  Anatomy
 Interstitial fluid osmotic pressure o biconcave discs with a diameter of 7–8 μm
(IFOP): Opposes BCOP which “pulls” o thickness: 2.5 mm
fluid out of capillaries into interstitial o average volume: 90-95 cubic L
fluid. o Plasma membrane: strong and flexible,
II. HEMATOPOIESIS allowing them to deform without rupturing as
they squeeze through narrow blood
capillaries.
A. DEFINITION AND OVERVIEW
o RBCs lack a nucleus and other organelles and
 The process by which the formed elements of blood
can neither reproduce nor carry on extensive
develop is called hemopoiesis or hematopoiesis.
metabolic activities.
 Where does Hematopoiesis happen? o Cytosol of RBCs: contains hemoglobin
First Trimester: Yolk sac molecules
Mid Trimester Gestation: liver, spleen, thymus, and
 Physiology
lymph nodes
o Red blood cells are highly specialized for their
Last trimester: Red bone marrow, and continues as
oxygen transport function.
the source of blood cells after birth and throughout
o Having no nucleus: they have all of their
life.
internal space available for oxygen transport.
 Red bone marrow: a highly vascularized connective
tissue.
PHYSIOLOGY
CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia

o Their Lack of mitochondria: generates ATP o Ruptured red blood cells: removed from
anaerobically (without oxygen) and they do circulation and destroyed by fixed phagocytic
not use up any of the oxygen they transport. macrophages in the spleen and liver
o Biconcave disc: gives greater surface area for o breakdown products are recycled and used in
the diffusion of gas molecules into and out of numerous metabolic processes, including the
the RBC than sphere or a cube. formation of new red blood cells.
o Major Function: transport of Hemoglobin, *NOTE: flow chart for the the RBC Life cycle (figure 3) is
which carries oxygen on summary page.
o Other functions:
 contains large quantity of Carbonic C. RBC ERYTHROPOIESIS
Anhydrase. A catalyst for reversible
reaction between CO2 and H2O to form  Erythropoiesis:
Carbonic acid making it an excellent o the production of RBCs
transporter of CO2 for expulsion. o Stimulated by Hypoxia
 Hemoglobin: buffer of the whole blood.  decrease blood volume
 Concentration of RBC in the Blood  poor blood flow
o In healthy men: average of 5.2x10^6/cubic ml  increase altitude
o In women: 4.7x10^6/cubic ml  pulmonary diseases
o Inhibited by rise in circulating RBC level
 Hemoglobin inside the cell o controlled by circulating hormone -
erythropoietin
o RBCs: can concentrate hemoglobin to
o starts in the red bone marrow with a precursor
34g/ 100 milliliters of cells.
cell called a proerythroblast
o If hemoglobin and hematocrit (the o Proerythroblast divide several times,
percentage of blood that is in cells— producing cells that begin to synthesize
normally, 40 to 45 percent) are normal, then hemoglobin.
the whole blood contains: o First generation: called basophilic
 Men: 15g hgb/ 100 mL erythroblast, only small amount of hgb
 Women: 14g hgb/100 mL accumulated, with high affinity to basic dye.
o each gram of hemoglobin can combine with o Ultimately, a cell near the end of the
1.34 ml O2 if the hemoglobin is 100 percent development sequence ejects its nucleus and
saturated. becomes a reticulocyte
 Men: 20 ml O2/ 100 ml blood o Reticulocytes:
 Women: 19 ml O2/100 ml Blood  retain some mitochondria,
ribosomes, and endoplasmic
B. RBC LIFE CYCLE reticulum.
 Red blood cells live only about 120 days because  during this stage, they pass from
of the wear and tear their plasma membranes bone marrow into capillaries through
undergo as they squeeze through blood diapedesis
capillaries.  develop into mature red blood cells
 Without a nucleus and other organelles, RBCs within 1 to 2 days after their release
cannot synthesize new components to replace from red bone marrow
damaged ones.
 The plasma membrane: becomes more fragile
with age, are more likely to burst, especially as
they squeeze through narrow channels in the
spleen.
PHYSIOLOGY
CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia

o Loss of the nucleus causes the center of the

cell to indent, producing the red blood cell’s
distinctive biconcave shape.

Figure 4: Genesis of Erythrocyte

 Maturation of Red Blood Cells Requires

Vitamin B12 (Cyanocobalamin) and Folic Acid
o vitamin B12 and folic acid: important for final
maturation of the RBCs
o essential for the synthesis of DNA
o Lack of either of these causes abnormal and
diminished DNA and, consequently, failure of
nuclear maturation and cell division
 Tissue Oxygenation Is the Most Essential
Regulator
of Red Blood Cell Production.
o Conditions that decrease the quantity of oxygen
transported to the tissues ordinarily increase the
rate of RBC production.
o Destruction of major portions of the bone
marrow: by x-ray therapy, causes hyperplasia of
the remaining bone marrow, to supply the
demand for RBCs in the body.
o At very high altitudes:
quantity of oxygen in the air is decreased >> o Principal stimulus for RBC production in low
insufficient oxygen is transported >> RBC production oxygen state (Hypoxia) thus inducing the
is greatly increased to the tissues volume as well. production of erythropoietin by the kidneys.
o Formed Mainly in the Kidneys.
 Erythropoietin (EPO)  90 % EPO formed in the kidneys
o A glycoprotein with a molecular weight of about  remainder is formed mainly in the liver.
34,000 o Renal tissue hypoxia leads to increased tissue
levels of hypoxia-inducible factor–1 (HIF-1),
which serves as a transcription factor for a large
PHYSIOLOGY
CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia
number of hypoxia inducible genes, including the
erythropoietin gene. HIF-1 binds to a hypoxia
response element residing in the erythropoietin
gene, inducing transcription of messenger RNA
and, ultimately, increased erythropoietin
synthesis
D. HEMOGLOBIN FORMATION
 Its synthesis begins in the proerythroblast and
continues into the reticulocyte stage.
 Hb binds loosely and reversibly with O2
Figure 5: Mechanism of EPO in RBC production
 Heme + Globin= Hemoglobin Chain
 Hemoglobin chain x 4= hemoglobin molecule
 1 hgb: contains 4 Fe 2+ which can combine with 4
O2 molecules
 Iron Metabolism
 Quantity of Fe in the body:
o Iron – 4-5 grams
o 65% - hgb
o 15-30% - ferritin (Iron + Apoferritin)
o 4% - myoglobin
o 1% - other heme cpds
o 0.1% - with transferrin (iron + apotransferrin)
 Most important sources of Iron from diet is
from the hemoglobin and myoglobin from
meat.
 Transport
o Once absorbed, combines with
apotransferrin to form transferrin which is
transported in plasma
o Loosely bound for easy release to any tissue
in the body
o Delivery of oxygen is directly to the
mitochondria, where heme synthesis
happens.
 Storage
o
In cell cytoplasm, iron combines with
apoferritin to form ferritin, which can
combine with small or large amount of iron.
Ferritin is Stored iron.
 Hemosiderin: small quantities of Iron that is
extremely insoluble
 Daily loss of Iron
o Man: 0.6 mg Fe/day in feces
o Woman: an additional 1.3 mg Fe/day during
menstruation
 Regulation:
o When all apoferritin are used up in storage,
there is decrease in iron absorption in the
intestine, conversely, when there is depletion
in storage, an increase absorption will
happen.
o
Figure 6: Iron Transport and Metabolism
E. RBC DISORDERS
Maturation Failure
 Pernicious Anemia: Failure to Absorb Vit. B12
Cause:
o Gastric Atrophy: causes failure to produce
normal gastric secretions.
 The parietal cells of the gastric glands
secrete a glycoprotein called intrinsic
factor.
 intrinsic factor: combines with
vitamin B12 in food and makes the
B12 available for absorption by the
gut.
 It does this in the following way:
1. IF binds with B12. Protects it from
gastric secretions.
PHYSIOLOGY
CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia

2. IF binds to receptors in the Ileum. o precipitated hemoglobin: damages the cell

3. B12 is absorbed to the blood membrane, so the cells become highly fragile,
stream through pinocytosis. leading to serious anemia
 Folic Acid Deficiency
o Folic acid is a normal constituent o Hereditary Spherocytosis
of green vegetables, some fruits, and meats  rare inherited hemolytic anemia
(especially liver) resulting from the defect in the red cell
o Cause: gastrointestinal absorption membrane.
Abnormalities (i.e. Sprue)  cannot withstand compression forces
because of their spherical shape.
Anemia  are easily ruptured by even slight
 Aplastic Anemia compression at splenic pulp and some
Hematopoietic stem cell (HSC) disorder other tight vascular beds.
characterized by:
o Pancytopenia (anemia, neutropenia and o Erythroblastosis Fetalis
thrombocytopenia)  Rh-positive RBCs in the fetus are
o With markedly hypocellular bone marrow attacked by antibodies from an Rh-
(less than 30% cellularity). negative mother
o Causes:
6 “I” s of the causes of o Major effects of anemia:
aplastic anemia:  greatly increased cardiac output
1. Idiopathic  increased pumping workload on the
2. Ingestion of drugs and heart
chemicals Polycythemia
3. Idiosyncratic o Secondary Polycythemia
4. Irradiation  physiological polycythemia
5. Infections and  occurs in natives who live at high
6. Inherited. altitudes, where the atmospheric
 Iron Deficiency Anemia oxygen is very low. The blood count is
o due to deficiency of iron causing defective generally 6 to 7 million/mm3; this blood
heme synthesis. count allows these people to perform
o Appearance: Microcytic Hypochromic Red reasonably high levels of continuous
cell work even in a rarefied atmosphere.
o Causes of deficiency o Polycythemia vera (Erythmia)
 Dietary deficiency is the most common  Pathologic polycythemia
cause of IDA.  Which the RBC count may be 7 to 8
 In adult men and postmenopausal million/mm3 and the hematocrit may be
women, deficiency may be due to 60-70% instead of the normal 40-45%
chronic gastrointestinal blood loss.  caused by a genetic aberration in the
 Impaired absorption hemocytoblastic cells that produce the
 Hemolytic Anemia blood cells. The blast cells no longer stop
o Sickle cell anemia producing RBCs when too many cells are
 cells have an abnormal type of already present, which causes excess
hemoglobin called hemoglobin S production of RBCs.
 substitution of valine by glutamic acid in
6th position of beta chain.
o When hemoglobin is exposed to low
concentrations of oxygen, it precipitates into
long crystals inside the RBC
PHYSIOLOGY
CHAPTER 33: Red Blood Cells, Anemia,
and Polycythemia

RESOURCES

o Guyton and Hall Textbook of Medical Physiology

13th Edition
o Ganong’s Review of Medical Physiology 23rd
Edition
o Principles of Anatomy and Physiology 15th
edition, Tortora and Derrickson.