BLOOD PHYSIOLOGY

• Definition

• Blood is a specialized type of connective

tissue. It is made up of two parts formed
elements and non cellular part(plasma)
 Blood
• By the end of the lecture you should be able
to:
• State the composition of Blood
• State the function of red blood cells and
plasma
• Explain the function of hemoglobin in the
transport of oxygen
• State the function of macrophages and
lymphocytes
• To understand the value of blood as an
important factor in homeostasis
INTRODUCTION:
GENERAL CHARACTERISTICS OF BLOOD:

1. color: bright red  oxygenated (systemic)

dark red/purple  deoxygenated (venous)

2. pH: 7.35 -7.45

3. 0smolality : 285 -295 mOsm
4. Viscosity  3-4x more viscous than water
5. Almost all blood cells are found red bone marrow.
 BLOOD
FUNCTIONS:
Transport function
- nutrients glucose, AA, etc
- waste products urea, lactic acid , creatinine
gases O2 , CO2
electrolytes Na+ K+ Cl- Ca++
regulation
ph buffers
temperature
protection
infection WBC , antibodies
blood loss platelets, clotting
factors
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Centrifuged Blood Sample

Liquid (plasma)

“Buffy coat” (white blood cells and platelets)

Red blood cells

Peripheral Blood Smear

White blood
cells

Red blood cells

Platelets
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Capillary tube

Plasma = 55%

Buffy coat

Red cells = 45%

(hematocrit)

Plug
Composition
• Volume varies with size.
• Blood is about 8% of the total body weight.
• Average adult has 5 liters of blood
• Blood is 40-45% cells
• This is also known as the percent packed cell
volume
• 95% are red blood cells, remainder white blood
•cells and blood platelets
• The hematocrit is an indicator of anemia,
polycythemia, and other conditions.
• Blood is 55 -60% plasma
• water, amino acids, proteins, carbohydrates, lipids,
vitamins, hormones, electrolytes, wastes
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Blood

45% 55%

Formed elements Plasma

Platelets Red blood cells White blood cells Electrolytes Water Proteins Wastes Nutrients Gases
(4.8%) (95.1%) (0.1%) (92%) (7%)
Vitamins

Hormones

Neutrophils Eosinophils Basophils Monocytes Lymphocytes Albumins Globulins Fibrinogen N2 O2 CO2

(54–62%) (1–3%) (<1%) (3–9%) (25–33%)
Composition of Blood
PLASMA
CHARACTERISTICS:
1. Straw colored
2. mainly water (91-92%), plasma CHONs,
nutrients, gases, non-CHON nitrogen subs,
and electrolytes

FUNCTIONS
1. transport of nutrients, gases and vitamins
2. regulate fluid and electrolyte balance
3. maintain pH
PLASMA
PLASMA PROTEINS
1. most abundant dissolved substances in plasma
2. Three main plasma proteins:
a. albumin – 60% of plasma CHONs, made in the
liver and they help to maintain oncotic pressure, and
transport certain molecules such as bilirubin and fatty
acids.
b. globulins – 36% of plasma CHONs
i. alpha and beta – produced in the liver, transport
lipids and fat soluble vitamins
ii. Gamma globulins – made by lymph tissue, a type
of antibody
c. fibrinogen - 4% of plasma CHONs, made in the
liver, help in blood coagulation
PLASMA
NUTRIENTS AND GASES
1.Nutrients : amino acids, simple sugars, nucleotides
and lipids
2.Blood gases: oxygen and carbon dioxide
NONPROTEIN NITROGEN SUBSTANCES
1. contain nitrogen but are not proteins
2. include: urea, uric acid, creatine & creatinine
3. CHON digestion  amino acids
4. CHON & nucleic acid catabolism  uric acid & urea
5. creatine metabolism  creatinine
PLASMA
PLASMA ELECTROLYTES
1. Electrolyte release ions when dissolved in water
2. include: sodium, potassium, calcium, magnesium,
chloride, bicarbonate, phosphate and sulfate
ions
3. Function:
maintain osmotic pressure and the pH
of the plasma.
Blood Cells
•Blood cells originate in red marrow from
hemocytoblasts or hematopoietic stem cells
• Stem cells can then:
• Give rise to more stem cells
• Specialize or differentiate

HEMATOPOIESIS - making of blood cells

ERYTHROPOIESIS - making of RBC
LEUKOPOIESIS - making of WBC
PLURIPOTENTIAL HEMATOPOIETIC STEM
CELLS
Hematopoiesis
Blood vessel White blood cell
Red blood
cell

platelet

Plasma
PRODUCTION OF RBC:
Early embryonic life : nucleated RBC  yolk sac
Middle trimester: liver main organ for production,
some are produced in the spleen and lymph nodes
Last month of gestation and after birth: exclusively
produced in the bone marrow
Bone marrow of essentially all bones produces RBCs
until 5 years old
Bone marrow of the long bones, except proximal portions
of the humeri and tibiae no RBCs after
20 yrs old
>20 yo membranous bones , like
vertebrae, sternum, ribs, ilia  less productive as age
increases.
GENESIS OF RBC
FUNCTIONS OF RBC
To transport Hemoglobin, which carries oxygen
from the lungs to the tissues
As an enzyme that catalyzes the reversible reaction
between carbon dioxide (CO2) and water to form
carbonic acid (H2CO3) carbonic anhydrase
As an excellent acid-base buffer
 Characteristics of Red Blood
Cells
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Top view

Red blood cells are:

•Erythrocytes
•Biconcave discs
7.8 micrometers

•Able to readily squeeze

through capillaries 2.5 micrometers
•Lack nuclei and mitochondria
•average volume: 90 -95 cubic (a)
Sectional view

micrometers
•Normal men: 5,200,00 cubic mm
•Normal women: 4,700,00 cubic
mm

(b)
RED BLOOD CELLS
Concentrate Hemoglobin (Hgb) in the cell fluid:
34 grams in each 100 milliliters of cells
Hematocrit ( % of blood that is cells – normally , 40-
45%) and the quantity of Hgb
 men : 15 grams of Hgb/100ml of cells
 women: 14 grams Hgb/100ml of cells
Each gram of pure Hgb  1.34 ml of Oxygen
Normal man: 20ml of O2/100ml of blood
Normal woman: 19 ml of O2/100 ml of blood
REGULATION OF RBC
Regulated within narrow limits:
1.adequate number is always available to provide
sufficient transport of O2
2.cells do not become so numerous that they
impede blood flow
Tissue oxygenation is the most essential regulator of
RBC
Red Blood Cell Production & Its Control
Low blood oxygen
Release into
•Low blood oxygen bloodstream

causes the kidneys and Liver Kidney Stimulation

the liver to release Inhibition

erythropoietin (EPO) –
which stimulates RBC
Erythropoietin
production
•This is a negative Increased
oxygen-
feedback mechanism Bloodstream
carrying
capacity

•Within a few days

many new blood cells Increased
number of
red blood
appear in the +
cells

circulating blood Red bone marrow

ERYTHROPOIETEN
A glycoprotein, molecular wt 34,000
90% kidneys; 10% liver
Epi or norepi will also stimulate erythropoietin
Maximum production within 24hours 5 days
Stimulation of the erythroblast
Dietary Factors Affecting Red Blood Cell
Production
• Vitamin B12 and folic acid are necessary
•They are required for DNA synthesis making them
necessary for the growth and division of all cells
• Iron is also necessary
• It is required for hemoglobin synthesis
Formation of hemoglobin
Synthesis of hemoglobin begin in the
proerythroblast and continues into Reticulocyte
Hemoglobin molecule compose of 4 hemoglobin
chains
There are four different chains of hemoglobin
(alpha, beta, gamma and delta chain)
Hemoglobin A is a combination of two alpha and
two beta chain
FORMATION OF HEMOGLOBIN
 HEME SYNTHESIS

8
Succinyl CoA

8 Glycine**

Heme

** Amino acid (building blocks of protein) synthesized in your body

STRUCTURE OF HEME

Ferrous iron (Fe2+)

Protoporphyrin IX:
contains 4 pyrrole
rings linked together
by methenyl bridges
 Note the 4 protein chains
that make up 1 molecule of
Hb.

Note that, in muscle, myoglo

(Mb) binds oxygen. Mb consis
of only 1 protein chain.

Fig. 14.8
 Mechanism of Transport
HEMOGLOBIN

* 4 Heme Molecules =
* 4 Oxygen Molecules

*Oxygenated Hemoglobin
Bright Red (systemic)
*Deoxygenated Hemoglobin
Blue (venous circulation)
Formation of hemoglobin
There are 4 iron atom in each hemoglobin
molecule. Each can bind one molecule of oxygen
that can be transported in each hemoglobin
molecule
Normal iron metabolism:

-The primary function is oxygen transport.

-Iron is absorbed by duodenum and jejunim
-Average total body iron content 4000-5000 mg.
- 65% in the form of HGB, 4% myoblogin, 1% heme cpd
-Iron is also stored in RE cells (BM, Spleen and liver) as
hemosiderin and ferritin.
-Also iron found in myglobin and myeloperoxidase and in
certain electron transfer.
-Iron is more stable in ferric state (Fe+++) than in ferrous
state (Fe++).
 Overview of Normal Iron Metabolism
Iron Tansport
Via transferrin

Iron Storage (Hepatic - major site)

Hepatic uptake of transferrin bound Fe via
classic transferrin receptor TfR1 (& homologous TfR2)
Hepatocytes are storage reservoir for iron
Taking up dietary iron from portal blood
Releasing iron into the circulation via ferroportin in times
of increased demand

Iron Utilisation
Erythropoiesis for haem synth / general cellular
respiration
Normally the body stores iron but women need to
consume more iron than men. Why?
Absorption, transport, and storage of iron
BLOOD
Stercobilin
CELLS Urobilin
excreted in feces
Hemoglobin excreted in urine

Globin
Urobilinogen
Heme
O2 formed by bacteria KIDNEY
reabsorbed
Heme oxygenase INTESTINE into blood
CO

Biliverdin IX via bile duct to intestines

NADPH
Biliverdin Bilirubin diglucuronide
reductase (water-soluble)

NADP+ 2 UDP-glucuronic acid

Bilirubin Bilirubin
(water-insoluble) LIVER
(water-insoluble) via blood
to the liver

Figure 2. Catabolism of hemoglobin

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Red bone
Bone marrow Nutrients
from food
2 Blood transports
3 Red blood absorbed nutrients
cells produced Vitamin B12
1 Absorption Folic acid
Iron
4 Red blood cells
circulate in
bloodstream for
about 120 days

5
Macrophage Old red
blood cells

Blood 6 Hemoglobin

Globin + Heme

7 Iron + Biliverdin
Bile
Liver Small
Bilirubin intestine
8
Too few, Too many
Anemia – low hematocrit (below-normal oxygen-
carrying capacity of the blood)
Nutritional, pernicious, aplastic, renal, hemorrhagic,
hemolytic
Polycythemia- abnormally high hematocrit (too
many RBCs in circulation)
Primary, secondary
 ANEMIAS
Blood Loss Anemia
-after hemorrhage , replaces the fluid portion of the
plasma in 1 to 3 days.
-cell concentration usually returns to normal within 3
to 6 weeks.
-chronic blood loss - microcytic,hypochromic anemia
Aplastic Anemia
- Bone marrow aplasia means lack of functioning bone
marrow.
Megaloblastic Anemia
-deficiency of vitamin B12, folic acid, and intrinsic factor from
the stomach mucosa
-atrophy of the stomach mucosa, as occurs in pernicious
anemia, or loss of the entire stomach after surgical total
gastrectomy
 ANEMIAS
HEMOLYTIC ANEMIA
1. hereditary spherocytosis
the red cells are very small and spherical rather
than being biconcave discs.
2. sickle cell anemia
present in 0.3 to 1.0 % of West African and
American blacks
the cells have an abnormal type of hemoglobin
called hemoglobin S, containing faulty beta chains in
the hemoglobin molecule
3. erythroblastosis fetalis
Rh-positive red blood cells in the fetus are
attacked by antibodies from an Rh-negative mother.
GENESIS OF RBC
Effects of Anemia on Function of the
Circulatory System
Increased cardiac output
Increased pumping workload of the heart
during exercise, which greatly increases tissue
demand for oxygen, extreme tissue hypoxia
results, and acute cardiac failure ensues.
 POLYCYTHEMIA
Secondary Polycythemia
> too little oxygen in the breathed air, such as at high
altitudes, or because of failure of oxygen delivery to the
tissues, such as in cardiac failure, the blood-forming
organs automatically produce large quantities of extra
red blood cells.
> RBC counts 6 to 7 million/mm3, about 30 % above
normal.
>physiologic polycythemia, occurs in natives who live
at altitudes of 14,000 to 17,000 feet, where the
atmospheric
oxygen is very low.
 POLYCYTHEMIA
Polycythemia Vera (Erythremia)
> pathological condition known in which the red
blood cell count may be 7 to 8 million/mm3 and the
hematocrit may be 60 to 70 per cent.
> caused by a genetic aberration in
hemocytoblastic cells that produce the blood cells.
> not only does the hematocrit increase, but the
total blood volume also increases, on some
occasions to almost twice normal.
> the viscosity of the blood increases from the
normal of 3 times the viscosity of water to 10 times
that of water.
Effect of Polycythemia on Function of
the Circulatory System

increased viscosity of the blood , blood flow through

the peripheral blood vessels is often very sluggish

decreases the rate of venous return to the heart.
Conversely, the blood volume is greatly increased in
polycythemia,
which tends to increase venous return.
cardiac output in polycythemia is not far from normal
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(a)

(b)
a: © The McGraw-Hill Companies, Inc./Al Telser, photographer :b © E d Reschke 53
WHITE BLOOD CELLS
 Blood Cell Origin and Production

Bone Marrow

Circulation

Figure 11-8
 5 - Types of WBC’s

Agranulocytes Granulocytes

Each WBC has a specific function

 White Blood Cells
(Leukocytes)
Mobile units of body’s defense system:

“Seek and Destroy” Functions:

1. Destroy invading microorganisms
2. Destroy abnormal cells (ie: cancer )

Clean up cellular debris (phagocytosis)

3. Assist in injury repair
Phagocytosis
WBC function is phagocytosis which means
cellular ingestion of the offending agent
Phagocytes is selective of the material that is
phagocytized and depends on:
1. Tissue surface structure
2. Protein coats
3. Development of antibodies
This selection of phagocytosis called
opsonization
Characteristics of WBC
White Blood Cells enter the tissue spaces by
Diapedesis.
Neutrophils and monocytes can squeeze through
the pores of the blood capillaries by diapedesis.
White Blood Cells move through tissue spaces
by Ameboid Motion.
White Blood Cells are attracted to inflamed
tissue areas by Chemotaxis
Epithelia

Fig. 14.14
Protect against infection: phagocytize bacteria; produce proteins that destroy
foreign particles
Diapedesis: leukocytes can squeeze between cells and leave the circulation
Infection
Characteristics of WBC
The adult human 7000 WBC/ ml of bld (in
comparison with 5 million red blood cells).(NV:
5,000 – 6,000)
The normal percentages of the different types are
Polymorphonuclear neutrophils 62.0% (54 -62%)
Polymorphonuclear eosinophils 2.3% (1 -3%)
Polymorphonuclear basophils 0.4% ( 0.5 -
1%)
Monocytes 5.3% (3 – 8%)
Lymphocytes 30.0% ( 25-
35%)
Characteristics of WBC
The life of the granulocytes normally 4 to 8 hours
circulating in the blood and another 4 to 5 days in
tissues .
The monocytes  short transit time, 10 to
20 hours in the blood, before wandering through the
capillary membranes into the tissues.
Once in the tissues, they swell to much larger sizes
to become tissue macrophages, and, in this
form, can live for months
 Types of WBC’s

Polymorphonuclear Granulocytes
1.Neutrophils
2.Eosinophils
3.Basophils
 1. NEUTROPHILS
* 54 -62% of all leukocytes
(most abundant of WBC’s)

* Important in
inflammatory responses

* Phagocytes that
engulf bacteria and
Debris
 2. EOSINOPHILS

* 1 -3 % of the WBC's

* Attack parasitic worms

* Control inflammation and allergic reactions

 3. BASOPHILS
* 0.5 - 1% of the WBC's

•Releases histamine and

heparin
Important in
Allergic
Reactions

* Heparin anticoagulant and helps clear fat

from
 Types of WBC’s

Mononuclear Agranulocytes
4.Monocytes
5.Lymphocytes
(B and T cells)
 4. MONOCYTES

* 3 - 8 % of the WBC's

* Exit blood (diapedesis)

to become macrophages

* Phagocytic = defend against

viruses and bacteria
 5. LYMPHOCYTES
* 25-35 % of the WBC's

* B-lymphocytes:
Produce Antibodies

* T-lymphocytes:
Directly destroy virus-
invaded cells and cancer
cells
Charateristics
Both Neutrophils and Macrophages can kill bacteria.
- contain bactericidal agents that kill most bacteria
Some bacteria have protective coats or other factors that
prevent destruction, killing results from oxidizing agents
formed by enzymes in the membrane
These oxidizing agents include large quantities of
superoxide (O2–), hydrogen peroxide (H2O2), and
hydroxyl ions (–OH–), all of which are lethal to most
bacteria, even in small quantities.
Also, lysosomal enzymes, myeloperoxidase, catalyzes
the
reaction between H2O2 and chloride ions to form
hypochlorite, which is exceedingly bactericidal.
Monocyte-Macrophage Cell System
(Reticuloendothelial System)

The total combination of

monocytes,mobile, macrophages, fixed tissue
macrophages, and a few specialized endothelial
cells in the bone marrow, spleen, and lymph nodes is
called the reticuloendothelial system.
all or almost all these cells originate from monocytic
stem cells; therefore, the reticuloendothelial system
is almost synonymous with the monocyte-
macrophage system.
Tissue macrophages in the skin and subcutaneous
tissues  Histiocytes
Macrophages (Kupffer Cells) in the liver sinusoids
Inflammation: Role of Neutrophils &
Macrophages
Tissue macrophages is the First Line of defense
against infection
Neutrophil invasion of the inflamed area is a Second
Line of Defense.
Second Macrophage invasion into the inflamed
tissue is a Third Line of Defense. Along with the
invasion of neutrophils.
Increased production of granulocytes and monocytes
by the Bone Marrow Is a Fourth Line of Defense
Blood vessel White blood cell
Red blood
cell

Platelets
Plasma
3. Platelets (Thrombocytes)

* Cell fragments bound to megakaryocytes

* “Bud Off” and are released into the blood
CHARACTERISTICS OF PLATELETS
CHARACTERISTICS:
1. Fragment of cells
2. round cell that lacks a nucleus
3. half size of the RBC
4. life span = around 10 days
Platelet count: NV 140,000 – 440,000/cumm
FUNCTION:
1.Release serotonin which contracts smooth
muscle in the
blood vessel reducing the flow of blood and
will begin
the formation of a blood clot
Function of Platelets
Stop bleeding from a damaged vessel
* Hemostasis

Three Steps involved in Hemostasis

1. Vascular Spasm
2. Formation of a platelet plug
3. Blood coagulation (clotting)
Steps in Hemostasis
*DAMAGE TO BLOOD VESSEL LEADS TO:
1. Vascular Spasm:
• Immediate constriction of blood vessel
• Vessel walls pressed together – become
“sticky”/adherent to each other

• Minimize blood loss

Steps in Hemostasis

2. Platelet Plug formation: (figure 11-10)

a. PLATELETS attach to exposed collagen
b. Aggregation of platelets causes release of
chemical mediators (ADP, Thromboxane A2)
c. ADP attracts more platelets
d. Thromboxane A2 (powerful vasoconstrictor)
* promotes aggregation & more ADP

Leads to formation of platelet plug !

 Figure 11-10

(+) Feedback promotes formation of platelet Plug

 Final Step in Hemostasis

3. Blood Coagulation (clot formation):

“Clotting Cascade”
a. Transformation of blood from liquid to
solid
b. Clot reinforces the plug
c. Multiple cascade steps in clot formation
d. Fibrinogen (plasma proteTinhr)ombin
Fibrin
COMPLETE BLOOD COUNT
RBC 4.5 – 6
MILLION/cumm
HEMOGLOBIN 12 – 16 gm/dl
HEMATOCRIT 40 – 48 %
RETICULOCYTE < 1%
WBC 5,000 – 10,0000/
cumm
NEUTROPHIL 54 - 62%
EOSINOPHIL 1 – 3%
BASOPHILS <1%
LYMPHOCYTES 25 – 35%
MONOCYTES 3 – 9%
PLATELETS 140,000 –
THANK YOU!