Far Eastern University — Nicanor Reyes Medical Foundation

School of Medicine
Physiology A – Blood Physiology: RBC and Blood Typing

LECTURE OUTLINE - Liver – the main organ for production of RBCs during the
I. Functions of the blood middle trimester of gestation; some are also produced in
II. Components of the blood the spleen, and lymph nodes.
III. Hematopoiesis - All bone marrows – where RBCs are exclusively produced
A. The Red Blood Cells during the last month or so of gestation and after birth
B. The ABO Blood Group (until 5 years old)
C. The Rh Blood Group - Note: The marrow of the long bones, except for the
D. The Platelets proximal portions of humeri and tibiae, becomes quite
fatty and produces no more RBCs after about age 20 years.
FUNCTIONS OF THE BLOOD - Bone marrows of the skull, vertebrae, ribs, and sternum
- Homeostasis (flat bones) – most RBCs continue to be produced here
- Respiratory after about 20 years of age
- Nutritive
- Excretory
- Endocrinology
- Acid-base balance
- Regulation of blood volume
- Regulation of body temperature

COMPONENTS OF THE BLOOD

A. Plasma
 60% of blood volume
- Composition:
 Water
 Proteins
 Glucose
 Lipids  ERYTHROPOIESIS (Genesis of Red Blood Cells)
 Salts - The blood cells begin their lives in the bone marrow from a
 Gases single type of cell called the pluripotential hematopoietic
 Special plasma substances stem cell from which all the cells of the circulating blood
- Functions: are eventually derived.
 Imparts oncotic pressure
 Source of antibodies
 Necessary for coagulation
 Acid-base balance
 Formation of enzymes
 Transport of hormones and enzymes
 Specific gravity of plasma
B. Formed Elements
 40% of blood volume
 Red blood cells
 White blood cells
 Platelets

Normal blood volume:

o In adult males = 70kg – 5 Liters
- 3000mL – 60% Plasma
- 2000mL – 40% Formed Elements
o In adult females = 4.5 Liters
- 2700mL – 60% Plasma
- 1800mL – 40% Formed Elements

HEMATOPOIESIS
- The process by which blood cells are
- Committed stem cells – intermediate-stage cells; have
Red Blood Cells (Erythrocytes)
already become committed to a particular line of cells
- Non-nucleated, biconcave disks
- Its shapes can change as it squeezes through capillaries; a
a. Hemocytoblast
“bag” that can be deformed into almost any shape
- Stem cell that produces all types of blood cells
- Major function: to transport hemoglobin, which carries
b. Proerythroblast
oxygen, from the lungs to the tissues
- The first cell that can be identified as belonging to the
- Responsible for most of the acid-base buffering power of
RBC series
whole blood
- It matures to become the reticulocyte that will mature
- In healthy men, average number of RBSs/mm3 = 5,200,000;
to become the erythrocyte
in women = 4,700,000 (Note: Persons living at high
- As the cell matures, its hemoglobin concentration
altitudes have greater numbers of RBCs.)
increases, while its nucleus condenses along with its
endoplasmic reticulum.
 PRODUCTION
c. Reticulocyte
- Yolk sac – it is the source of primitive, nucleated RBCs of
- Contains a small amount of remnants of Golgi
the embryo in its early weeks
apparatus, mitochondria, and a few other cytoplasmic
organelles

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 Far Eastern University — Nicanor Reyes Medical Foundation
School of Medicine
Physiology A – Blood Physiology: RBC and Blood Typing
- During this stage, the cells pass from the bone marrow
into the blood capillaries by diapedesis or squeezing
through the pores of the capillary membrane.
 HEMOGLOBIN
- Synthesis of hemoglobin begins in the
proerythroblasts and continues even into the
reticulocyte stage of the RBCs.
- Hemoglobin formation:
1. 2 succinyl-CoA + 2 glycine  pyrrole molecule
2. 4 pyrroles  protoporphyrin IX
3. Protoporphyrin IX + Fe++  heme
4. Heme + polypeptide  hemoglobin chain ( or )
5. 2 chains  + 2  chains  hemoglobin A
- Each hemoglobin molecule can transport 4 molecules
of oxygen (or a total of 8 oxygen atoms).
 Clinical Correlation: Sickle Cell Anemia
- Abnormality in the chain of the hemoglobin molecule
- Blood disorder wherein RBCs change shape and cause
health problems
- The amino acid valine is substituted for glutamic acid at
one point in each of the two beta chains of the
hemoglobin chain. When this type of hemoglobin is
exposed to low oxygen, it forms elongated crystals
inside the RBCs that are sometimes 15 micrometers in
length. These crystals make it almost impossible for
the cells to pass through many small capillaries, and
the spiked ends of the crystals are likely to rupture the
cell membranes, leading to sickle cell anemia.
 IRON
- Important for the formation of hemoglobin and other
essential elements in the body (e.g. myoglobin,
cytochromes, cytochrome oxidase, peroxidase, and
catalase)
- 4 to 5g – total quantity of iron in the body
- 65% is in the form of hemoglobin, 4% is in the form of
myoglobin, 1% is in the form of various heme
compound that promotes intracellular oxidation, 0.1%
is combined with transferrin in the blood plasma, and
15-30% is stored for later use in the form of ferritin
- A man excretes about 0.6mg of iron each day, mainly
into the feces. Additional quantities of iron are lost
when bleeding occurs.
- For a woman, additional menstrual loss of blood brings
long-term iron loss to an average of 1.3mg/day.
 ABSORPTION OF IRON FROM THE INTESTINAL TRACT:
1. The liver secretes moderate amounts of apotransferrin into
the bile.
2. The apotransferrin binds with free iron and also with
certain iron compounds, such as hemoglobin and
myoglobin from meat (two of the most important sources
of iron in the diet). This combination is called transferrin.
3. Transferrin binds with the receptors in the membranes of
the intestinal epithelial cells.
4. By pinocytosis, the transferrin molecule, carrying its iron
store, is absorbed into the epithelial cells and later released
into the blood capillaries beneath these cells in the form of
plasma transferrin.
- Note: Iron absorption from the intestines is extremely slow,
therefore, even when tremendous amounts of iron is present
in the food, only small proportions can be absorbed.
 VITAMIN B12 AND FOLIC ACID
- Vitamins which are important for final maturation of
the RBCs
- Essential for the synthesis of DNA because each is
required for the formation of thymidine triphosphate
which is essential building blocks of DNA
- Lack of either Vitamin B12 or Folic Acid causes
abnormal and diminished DNA and failure of nuclear
maturation and cell division.
- Deficiency of these Vitamins also causes maturation
failure which results to the production of macrocytes or
irregular, larger than normal, and oval-shaped RBCs.
These poorly formed cells can still carry oxygen
normally but their fragility causes them to have a short
life (1/2 to 1/3 normal).
- Vitamin B12 – naturally found in animal products,
including fish, meat, poultry, eggs, milk, and milk
products
- Note: The minimum amount of Vitamin B12 required
each day to maintain normal RBC maturation is only 1
to 3 micrograms, and the normal storage in the liver
and other body tissues is about 1000 times this
amount. Therefore, 3 to 4 years of defective Vitamin
B12 absorption are usually required to cause maturation
failure anemia.
- Folic acid – normal constituent of green vegetables,
some fruits, and meats (especially liver); however, it is
usually destroyed during cooking
 CONTROL OF RED BLOOD CELL PRODUCTION
1. Stimulated by Hypoxia
 Most important regulator of RBC production
 Deficiency in oxygen
 Conditions that decrease the quantity of oxygen
transported to the tissues ordinarily increase the rate
of RBC production
 Can be caused by: anemia, destruction of major
portions of bone marrow (especially by x-ray therapy),
high altitudes, prolonged cardiac failure, lung
diseases
2. Stimulated by erythropoietin and its formation
increases in response to hypoxia
3. Inhibited by increase in circulating RBC levels
 LIFE SPAN OF RED BLOOD CELLS
- 120 days
- Mature RBCs do not have nucleus, mitochondria, and
endoplasmic reticulum
- Mature RBCs have enzymes that:
1. Metabolize glucose and form small amounts of
ATP
2. Maintain pliability of the cell membrane
3. Maintain membrane transport of ions
4. Keep the iron of the cell’s hemoglobin in the
ferrous form rather than ferric form
5. Prevent oxidation of the proteins in the RBCs
- Many of the RBCs self-destruct in the spleen
- Note: When the spleen is removed, the number of old
abnormal RBCs circulating in the blood increases
considerably.
 EFFECT OF DIFFERENT SOLUTION IN THE RBC
MEMBRANE
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 Far Eastern University — Nicanor Reyes Medical Foundation
School of Medicine
Physiology A – Blood Physiology: RBC and Blood Typing

- Hypertonic solution – RBC shrinkage/crenation - Note: The skin of a person with this condition usually
- Hypotonic solution – RBC swelling; eventually has ruddy complexion with bluish tint.
rupturing  Secondary Polycythemia
- Isotonic solution – no change; 0.9% NaCl; 5% - Occurs when the tissues become hypoxic because of
Dextrose too little oxygen in breathed air (such as in high
altitudes, smoking, having pulmonary diseases), or
 THE ANEMIAS failure of oxygen delivery to the tissues
- Deficiency of hemoglobin in the blood which can be - The blood-forming organs produce large quantities of
caused by either too few RBCs or too little hemoglobin extra RBCs
in the cells THE ABO BLOOD GROUP
- Major effects: increased cardiac output and increased
pumping workload on the heart
 Blood Loss Anemia
- Iron deficiency
- Occurs due to chronic blood loss
- RBCs cannot absorb enough iron from the intestines
to form hemoglobin as rapidly as it is lost
- Gives rise to microcytic, hypochromic anemia
 Bone Marrow Aplasia
- Lack of functioning bone marrow
- Can be caused by:
1. Exposure to high-dose radiation or chemotherapy for
cancer treatment which causes damage to the stem
cells of the bone marrow
2. High doses of certain toxic chemicals such as
insecticides or benzene in gasoline
3. Autoimmune disorders such as lupus erythematosus
(the immune system begins attacking healthy cells
such as bone marrow stem cells)
- Note: People with severe aplastic anemia usually die
unless they are treated with blood transfusions or by
bone marrow transplantation.
 Megaloblastic Anemia
- Lack or loss of vitamin B12 and folic acid causes slow
reproduction of erythroblasts in the bone marrow
resulting to large, odd-shaped RBCs called
megaloblasts. These cells rapture easily, leaving the
person in dire need of an adequate number of RBCs.
- Often develops in patients who have intestinal sprue,
in which folic acid, vitamin B12, and other vitamin B
compounds are poorly absorbed
 Hemolytic Anemia
- The life span of the fragile RBC is so short that the
cells are destroyed faster than they can be formed

 POLYCYTHEMIA
 Polycythemia Vera
- Caused by genetic aberration in the hemocytoblastic
cells that produces blood cells
- The blast cells no longer stop producing RBCs when too
many are already present
- Usually causes excess production of WBC and platelets
as well
- No inhibition of erythropoietin; no inhibition of
hemoglobin production
- Increase in RBCs does not inhibit further production of
erythropoietin
- Blood is prone to clotting