BLOOD C.

Platelets

⚫ A highly complex suspension of cells in a viscious fluid - small granulated bodies; 2-4 micra in diameter
medium
- fragments of the megakaryocyte
PHYSICAL CHARACTERISTICS
- about 300,000/cu.m of circulating blood
1. Accounts for approximately 8% of body weight
- function: to activate the blood clotting
Volume in healthy adult: mechanism

A. males (5-6L) - Thrombopoiesis is controlled by the hormone

Thrombopoietin
B. females (4-5L)
QUANTITY OF HEMOGLOBIN (Hgb)
2. pH: Slightly Alkaline; between 7.35 - 7.45
⚫ RBCs can concentrate Hgb up to about 34g in each 100mL
3. Viscosity: 5x more viscous than water because of its
of cells (metabolic limit of the cell’s hemoglobin-forming
formed elements
mechanism)
4. Color: ⚫ In normal people, the % of Hgb almost always near the
A. Scarlet - Oxygen-rich Arterial Blood maximum

B. Dark Red - Oxygen-poor Venous Blood ⚫ If hematocrit and Hgb in each cell are normal, then:

5. Sticky, Opaque fluid with a characteristic salty taste
FUNCTIONS
A. Distribution Functions
1. Delivery of oxygen from the lunch and of
nutrients form the digestive tract to all body cells
2. Transport of metabolic waste products from cells
to elimination sites (Lungs for elimination of CO2;
Kidney for elimination of nitrogenous wastes in
urine)
Men: Hgb of 15g/100mL
Women: Hgb of 14g/100mL
⚫ Each gram of hemoglobin can combine with 1.34mL of
oxygen
Men: 20 milliliters of oxygen can be carried in
combination with Hgb in each 100mL of blood
Women: 19 milliliters of oxygen can be carried in
combination with Hgb in each 100mL of blood
PRODUCTION OF RBCs

3. Transport of hormones from the endocrine
organs to their target organs
4. Maintenance of body temperature through the
absorption & distribution of body
B. Protection Functions
1. Maintenance of normal pH of body tissues
2. Maintenance of an adequate fluid volume in the
circulatory system
⚫ Embryonic life - yolk sac (nucleated RBC)
⚫ Middle Trimester - liver(main organ), spleen, lymph nodes
⚫ Third Trimester and After Birth - bone marrow
Postnatal Hematopoeisis:
> Bone marrow of essentially all bones produce RBCs until
about 5 years old; Marrow becomes fatty (except
proximal portions of humerus and tibia, which produce
RBC until age 20)

3. Prevention of blood loss > After age 20 - marrow of membranous bones (vertebrae,
sternum, ribs, ilia)
4. Prevention of infection

COMPOSITION OF BLOOD

1. Formed Elements - Cellular Elements = constitute 45%

of volume

A. Red Blood Cell (RBC)

- non-nucleated biconcave disc

- mean diameter: 7.8 micrometer
- thickness: 2.5 micrometer at thickest point; 1
micrometer or less at the center
*Marrow becomes less productive as age increases
GENESIS OF BLOOD CELLS
⚫ Pluripotential Hematopoeitic Stem Cells (PHSC)

- volume: 90-95 cubic micrometers
- concentration of RBC in the blood:
Normal Males: 5.2M/cu.mm +300,000
- cells in the bone marrow in which all the cells in the
circulating blood are derived
- as these cells reproduce, a small portion of them

Normal Females: 4.7M/cu.mm + 300,000

B. White Blood Cell (WBC)

- mobile units of body’s protective system

 remains exactly like the original pluripotential cells and is - 1st cell that can be identified as belonging to the RBC
retained in the bone marrow to maintain a supply of series; once formed, it divides multiple times forming
these, although their numbers decrease with age many mature RBC

- most of the reproduced cells differentiate to form the 2. Basophilic Erythroblasts/Basophilic

other cell types Normoblast/Prorubicyte

- the intermediate-stage cell of early offspring are very - 1st generation cells; stain with basic dyes; accumulated
much like with the pluripotential stem cells, even though very little Hgb
they have already committed to a particular line of cells -
Succeeding Generations
committed stem cells
⚫ Cells become filled with Hgb to a concentration of about
Colony-forming unit (CFU)
34%
CFU-E: produce erythrocytes
1. Nucleus condenses to a small size
CFU-M: produce platelets
2. Remnant is absorbed or extruded from the cell
CFU-GM: produce granulocytes and monocytes
3. Endoplasmic Reticulum is reabsorbed

3. Polychromarophilic Erythroblast/Polychromatophilic
Normoblast/Prorubicyte

4. Orthochromatic Erythroblast/ Orthochromatic

Normoblast/ Metarubricyte

5. Reticulocytes/ Diffusely Basophilic Erythroblast/

Polychromatophilic Erythrocyte

- remnants of RNA (Golgi Apparatus, Mitochondria, and a

few other cytoplasmic organelles)

- diapedesis: used as cells pass from the bone marrow

into the blood; squeeze through pores of the
capillary membrane

⚫ Growth Inducers - multiple proteins which control growth - 1 to 2 days (short life; concentration among all the red
and reproduction of different stem cells cells of the blood is normally slightly less than 1%)
Example:
6. Erythrocytes
Interleukin-3 promotes
growth and reproduction - most mature stage
of virtually all the different RED BLOOD CELLS
types of committed stem
cells ⚫ Lifespan of 120 days

⚫ Differentiate Inducers - promote ⚫ Contain cytoplasmic enzymes that are capable of

differentiation; causes one type of metabolizing glucose and forming small amounts of ATP
committed stem cell to
Enzymes:
differentiate one or more steps
toward a final adult blood cell -Maintain pliability of cell membrane
⚫ Growth and Differentiation Inducers - controlled by -Maintain membrane transport of iron
factors outside the bone marrow
-Keep iron in ferrous form
> RBC: exposure of the body to low oxygen for a long
period -Prevent oxidation of the proteins in the RBCs

> WBC: infectious diseases cause growth differentiation &
eventual formation of the specific types of WBC that are
needed to combat infection
STAGES OF DIFFERENTIATION OF RBC
Regulation of RBC Production
⚫ Total mass of RBC in the circulatory system is regulated
within narrow limits
1. Adequate red cells are always available to provide
sufficient transport of oxygen from the lungs to the
tissues

2. Cells do not become so numerous that they impede

blood flow

⚫ Tissue Oxygenation: basic regulator of the production

-Any condition that causes the quantity of O2 transported

to the tissues to decrease ordinarily increases the rate of
RBC production

1. Anemia: result of hemorrhage or any other condition,

the bone marrow begins to produce large quantity of RBC
1. Proerythroblast/Pronormoblast/Rubriblast 2. Destruction of Major Portions of the Bone Marrow:
 -causes hyperplasia of the remaining BM, attempting
to supply the demand of RBC in the body
3. High altitudes
-pressure of O2 decreases, insufficient oxygen
transport to the tissues
-red cell production is increased
4. Various diseases of the circulation that causes
decrease blood flow through the peripheral vessels &
particularly those that cause failure of O2 absorption also
increases RBC production
Ex: Prolonged cardiac failure in many lung diseases
(Hypoxia - increases the red cell production, increase
in hematocrit and total blood volume)
ERYTHROPOIETIN
⚫ Principal stimulus for RBC production in low oxygen state
⚫ Glycoprotein with a molecular weight of 34,000
⚫ Absence of erythropoietin = hypoxia has little or no effect
to stimulate RBC production/few RBC in the bone marrow
⚫ When functional, hypoxia causes a marked increase in
erythropoietin production and the erythropoietin
enhances RBC production until the hypoxia is relieved
⚫ Tissue oxygenation is the most essential regulator of RBC
production
⚫ At very high altitudes, oxygen in air is decreased and RBC
production is increased
⚫ 90% formed in the kidneys, 10% in the liver
⚫ Renal tissue hypoxia leads to increased tissue levels of
hypoxia-inducible factor-1 (HIF-1)
◼ HIF-1: serves as a transcription factor got a large
number or hypoxia-inducible-genes, including the
erythropoietin gene
◼ HIF-1-: binds to a hypoxia response element in the
erythropoietin gene - increased erythropoietin
synthesis
◼ Hypoxia in other parts of the body send signals to
the kidney to produce eryhtropoietin
◼ Norepinephrine, epinephrine, and several
prostiglandins stimulate erythropoietin production
⚫ Anemia: 2 kidneys are removed or destroyed by renal
disesases
Maturation of RBC
⚫ Requires Vitamin B12 (Cyanocobalamin) and folic acid
⚫ B12 and FA are essential for the synthesis of DNA because
each is required for the formation of thymidine
triphosphate, one of the essential building blocks of the
DNA
⚫ Lack of B12 and FA causes abnormal and diminished DNA
and failure of nuclear maturation and cell division -
Macrocytes (larger than normal RBCs, flimsy membrane,
fragile, irregular, oval)
HEMOGLOBIN
⚫ Synthesis of Hgb begins in the proerythioblast and
continues into the reticulocyte stage of the RBC
⚫ Each heme molecule combines with a long polypeptide
chain, a globin synthesized by ribosomes, forming a
subunit og Hgb called hemoglobin chain
⚫ Each chain has molecular weight of 16,000; 4 Hgb chains =
Hgb molecule
⚫ Each Hgb chain has a heme prosthetic group containing
an atom of iron
⚫ Each Hgb has 4 chains = 4
atoms of iron
⚫ Each iron molecule can bind
with one molecule of
oxygen
⚫ Hgb = 4 molecules of
oxygen or 8 atoms of
oxygen
⚫ Hgb chains are alpha, beta,
gamma, delta
⚫ Most common form of Hgb
is Hgb A = 2 Alpha and 2
Beta Chains
⚫ Types of Hgb chains determine the binding affinity of the
Hgb for oxygen
⚫ Abnormalities of the chains can alter the physical
characteristics of the Hgb molecule
Ex: Sickle Cell Anemia - valine is substituted for glutamic acid at
one point in each of the 2 beta chains
⚫ Primary function in the body is to combine with oxygen in
the lungs and then release this oxygen readily in the
peripheral tissue capillaries, where the gaseous tension of
oxygen is much lower than in the lungs
IRON
⚫ Important for the formation not only of hemoglobin but
also of other essential elements in the body
⚫ Total body quantity - 4 to 5 grams
◼ 65% in Hemoglobin
◼ 4% in Myoglobin
◼ 1% in various heme compounds
◼ 0.1% combined with the protein transferrin in the
blood plasma
◼ 15-30% stored for later use
ANEMIA
⚫ Deficiency of Hgb in the blood, which can be caused by
either too rapid loss or too slow production of RBCs or too
little Hgb
A. Blood Loss Anemia (Hemorrhagic Anemia)
- due to rapid hemorrhage; fluid portion of plasma replaced in
1-3 days(leaves a low concentration of RBC), RBC normal within
3-6 weeks
- when Chronic blood loss occurs, inadequate iron absorption
to replace RBC loss - Microcytic, Hypochromic Anemia
➢ Acute Hemorrhagic Anemia - following a severe wound
➢ Chronic Hemorrhagic Anemia - slightlty persistent blood
loss, as might result from hemorrhoids or undiagnosed
bleeding ulcer
➢ Once the primary problem is resolved normal
erythropoietic mechanism replace the deficient cells
B. Aplastic Anemia (Bone Marrow Aplasia)
- bone marrow is not functioning
- due to bone marrow dysfunction, persons exposed to gamma
ray radiation excessive X-ray treatment, certain industrial
chemicals and drugs which the person might be sensitive
-leads to stem cell damage; due to autoimmune diseases
- in half of aplastic anemia cases the cause is unknown, a
condition called Idiopathic Aplastic Anemia
C. Megaloblastic Anemia
- vitamin B12, Folic Acid deficiency and intrinsic faactor
deficiency
- slow reproduction of erythroblasts in the bone marrow
- cell grow large with odd shapes, called Megaloblasts
- Pernicious Anemia or loss of the entire stomach after the
surgical total gastrectomy can lead to this
D. Hemolytic Anemia
- normal production of RBC life span is short due to different
abnormalities of the RBC which maybe hereditary, acquired,
and make cells very fragile so they rupture easily
Examples:
➢ Hereditary Spherocytosis
- red cells are very small and spherical rather than being
biconcave discs
- cannot withstand compression forces because they do
not have normal physical structure of a cell
- ruptures when compressed
➢ Sickle Cell Anemia
- has an abnormal type of Hgb, Hemoglobin S, containing
faulty beta chains in the hemoglobin molecule
- Hgb S precipitates into long crystals inside the RBC when
it is exposed to low concentration
- precipitated Hgb can also damage the cell membrane,
cells become fragile, leading to Anemia
➢ Erythroblastosis Fetalis
-Rh positive RBCs in the fetus are attacked by antibodies
from an Rh negative mother
➢ Thalassemias
- thin and delicate RBCs (RBC count less than 2M/ cu.mm)
Effects of Anemia on Circulatory System
➢ In severe anemia, blood viscosity may fall to as low as
1.5x that of water (Normally, 3x that of water). The
decreased viscosity decreases the resistance to blood flow
in the peripheral blood vessels which causes increase
blood flow to the tissues and increased blood return to
the heart
➢ Hypoxia causes peripheral tissue blood vessels to dilate,
allowing a further return of blood to the heart and
increasing the cardiac output
➢ Anemia leads to greatly increased cardiac output and
increased pumping workload on the heart
POLYCYTHEMIA
⚫ Increased amounts of RBC in circulation
⚫ Secondary Polycythemia
- secondary to tissue hypoxia
- blood forming organs automatically produce large
quantities of extra RBC
- RBC count rises to 6-7M/cubic mm, 30% above normal
> Physiological Polycythemia
- occurs in native who live at altitude of 14,000 to
17,000 feet, atmospheric oxygen is very low
- blood count: 6-7M/cubic mm
- allows people to perform high levels of continuous
work even in a rarefied atmosphere
⚫ Polycythemia Vera (Erythremia)
- RBC count may be up to 7-8M/ cubic mm and the
hematocrit may be 60-70% instead of the normal 40-45%
- caused by a genetic aberration ( BLAST CELL: never stop
producing red cells) in the hemocytoblastic cells that
produce the blood cells
- total blood volume increases; the entire vascular system
becomes intensely engorged
- blood capillaries become plugged by the viscous blood
- the viscosity of the blood in polycythemia vera
sometimes increases from the normal of 3 times the
viscosity of water to 10 times of that water
Effects of Polycythemia on Circulatory System
⚫ Blood flow through the peripheral blood vessels is
sluggish
⚫ Increasing blood viscosity decreases venous return to the
heart
⚫ Increased blood volume increases venous return to the
heart
⚫ Arterial pressure may be released
⚫ Ruddy complexion with a bluish(cyanotic) tint to the skin
Blue - deoxygenated
Red - oxygenated
WHITE BLOOD CELLS
⚫ Mobile units of the body’s protective system
⚫ Acting together, these cells provide the body with  Tissue macrophage system - provides a first line of
powerful defenses against tumors, viral infections, defense in the tissues against infection
bacterial infections, parasitic infections
Examples:
⚫ 4,000-11,000/cu.mm
> Histiocytes - skin and subcutaneous tissues
⚫ Formed partially in the bone marrow and partially in the
>Tissue Macrophage - lymph nodes
lymph nodes
>Alveolar Macrophages - lungs
⚫ Transported in the blood to different parts of the body
where they are needed >Kuffler Cells - liver
⚫ Provide a rapid and potent defense against infectious >Microglia - brain
agents
⚫ Granulocytes and Monocytes: protect the body against
Types of WBC invading organisms mainly by ingesting them
➢ Granulocytes ⚫ Lymphocytes and Plasma Cells: mainly in connection with
the immune system
- polys - multiple nuclei
⚫ Life span of granulocytes once released from the bone
1. Neutrophil
marrow is 4-8 hours circulating in the blood and another
-Most numerous of the WBC 4-5 days in the tissues; it will be shortened though in
infection; ingest the invading organisms in the process are
-Exhibit phenomenon of chemotaxis (attraction to
themselves destroyed
the injuries site)
Production and Life Span of Leukocytes
-Neutrophilia and neutrophil invasion of the
inflamed area -> 2nd line of defense against infection ⚫ Leukopoiesis is hormonally stimulated;
Hematopoietic hormones-Colony Stimulating Factors(CSF);
2. Eosinophil
not only prompt the WBC precursors to divide and mature
-Slightly phagocytic but also enhance the protective potency of mature
leukocytes
-Plays a part in detoxification ang also in the
disintegration and removal of proteins ⚫ WBC are able to slip into and out of the blood vessels by
Diapedesis
-Increase in number in parasitic infection and allergy
attacks Concentration of the Different WBC in the Blood

3. Basophil ⚫ Adult human being has about 7000 WBC per microliter of
blood
-Exhibit local anticoagulant in cases of inflammation
and this ability is due to its elaboration of a heparin ⚫ Total WBC, normal % in diff. WBCs:
like subs
1. Polymorphonuclear Neutrophils - 62.0%
-Least numerous WBC
2. Polymorphonuclear Eosinophils - 2.3%
➢ Agranulocytes
3. Polymorphonuclear Basophils - 0.4%
1. Lymphocytes
4. Monocytes - 5.3%
-Concerned with the formation of gamma-globulin
5. Lymphocytes - 30.0%
which now serve as Ab’s
*Platelets: 300,000
-Remain in the blood for a few hours -> pass by
diapedesis into the tissues, then reenter the lymph
and return to the blood again

-Life span varies from 100 to 300 days or in some

even years depending on the body’s need

2. Monocytes

-Phagocytes

-Mobilized along with neutrophils as part of the

inflammatory response

-Constitute a first line defense against bacterial

infection

-Has short transit time in the blood before

wandering through the capillary membrane into the
tissues; swell to much larger size to become tissue
macrophage and can live for months-years unless
destroyed by performing phagocytic function

* Platelets: fragments of another type of cell similar to the

WBC found in the bone marrow, megakaryocyte; activate
the blood clotting mechanism
 - more differentiated, more chronic is the leukemia; 10-20
years

- especially the very undifferentiated cells are usually non

functional, so that they can’t provide the usual protection
associated with WBCs

Types of Leukemia

 Lymphogenous Leukemia

◼ Cause by cancerous production of lymphoid cells,

beginning first in the lymph node or other
lymphogenous tissue then spreading to other areas
of the body

 Myelogenous Leukemia

◼ Begins by cancerous production of lymphoid cells in

the bone marrow and then spread throughout the
body so that the WBCs are produces in many
extramedullary organs

Effects of Leukemia on the Body

⚫ 1st: Metastatic growth of leukemic cells in abnormal areas

Process of INFLAMMATION
⚫ When tissue injury occurs, multiple substances that
causes dramatic secondary changes in the tissues are
released by the injured tissues
⚫ Inflammation: Secondary changes
- Vasodilation of the local blood vessels
- Increases permeability of the capillaries with leakage of
large quantities of fluid into the interstitial spaces
- Often clotting of the fluid in these spaces because of
excessive amounts of fibrinogen & other proteins
of the body; leukemic cells from the bone marrow may
reproduce so greatly that they invade the surrounding
bone, causing pain and a tendency for bones to fracture
easily
⚫ Spread on the spleen, lymph nodes, liver and other
vascular organs
⚫ Development of infection and bleeding tendency caused
by thrombocytopenia (lack of platelets)
⚫ Excessive use of metabolic substrates by the growing
cancerous cells
⚫ Utilize the metabolic elements of the tissues & cause
tissue destruction

- Migration of large numbers of granulocytes and

monocytes into the tissue

- Swelling of the cells

Walling-Off Effect of Inflammation

- One of the 1st results of inflammation is to “wall-off” the

area of injury from the remaining tissues; delays the
spread of bacteria or other toxic products

- Pus: mixture of necrotic tissue, dead neutrophils & dead

macrophages

- Agranulocytosis: clinical condition where in the bone

marrow stops producing WBC, leaving the body
unprotected against bacteria & other agents that might
invade the tissues

LEUKEMIAS

⚫ Uncontrolled production of WBC caused by cancerous

mutation of a myelogenous and lymphogenous cell

⚫ Increased numbers of abnormal WBC in the circulating

blood

➢ Leukemic Cells

- bizarre and undifferentiated and not identical to any of

the normal WBC

- the more undifferentiated the cell, the more acute is the

leukemia; death when untreated