10. Physiology is
The study of the function of all plants
and animals in their normal state.
an integrative science
10
Figure 1-1: Levels of organization and the related fields of study
12. Human Physiology. In human
physiology, we attempt to explain
the specific characteristics and
mechanisms of the human body
that make it a living being.
⢠The goal of physiology is to explain the
physical and chemical factors that are
responsible for the origin, development,
and progression of life.
12
15. Distinguish between Process & Function
How do we breathe? Why do we breathe?
How does blood Why does blood
flow? flow?
How do RBCs Why do RBC
transport O2? transport O2?
Integrate both for complete picture! 15
16. Key Themes in Physiology:
1. Homeostasis
Body systems work together (Integration of
function)
Internal vs. external failure of homeostasis
1. Communication and movement across cell
membranes
Vital to integration & homeostasis
Cells communicate with other cells, tissues
& organs
16
17. Energy Flow and Law of Mass
Balance
Major routes
for input?
All living processes require
constant input of energy
Where from? - How is it stored?
How is it used to do work?
Major routes
for output?
Total amount of substance in body = intake + production - output
What substances are maintained through law of mass balance?
17
19. What is Blood?
⢠A dynamic, life-sustaining
solution in animals with
closed circulatory systems
⢠containing
⢠1. ions,, nutrients, waste
products, hormones, other
substances,
⢠2. cells.
⢠Blood cells and platelets -
are suspended in plasma.
19
20. Basic facts
⢠One of body organ
⢠Fluid in nature
⢠Red in color
⢠Total circulating blood volume is about 8%
of body weight
⢠5.6 liter in 70 Kg man
⢠(4 to 5 liters in normal Female & 5-6 liters
in normal male )
⢠About 55% of this volume is plasma
⢠Connective tissue in nature Dr Alamzeb MBBS M.Phil
20
31. Composition of Blood
Blood consist of
1 Red cell
2 White cell
3 Platelets
4 Plasma â
in which the above elements are suspended
Plasma is the liquid component. which contain
soluble fibrinogen
Serum is what remains after the formation fibrin clot
Dr Alamzeb MBBS M.Phil
31
32. BLOOD
⢠Your circulatory system contains about 5 liters of the
most remarkable fluid on earth,
⢠traveling through 65,000 miles(104650)Kms of blood
vessels to carry oxygen and nutrients to every one of
your 100 trillion cells,
⢠and remove waste products from them.
⢠45% of the volume is red blood cells (RBCs) which
make round trips to your big toe about every 20
seconds,
⢠flowing through capillaries just 1/10th the diameter of a
human hair where the transfer takes place...so small
that only one RBC at a time can wriggle through.
Dr Alamzeb MBBS M.Phil 32
33. BLOOD.
Blood is also vital to maintain a
stable body temperature by varying
the amount of blood to different
areas of the body.
To do all this, the heart pumps about 2,000
gallons (9100 liters) of blood per day;
its valves operate some 5000 times
per hour, and it never stops for
maintenance...not even once!
The Bible said a long time ago that
"the life of the flesh is in the
blood." Dr Alamzeb MBBS M.Phil
33
35. RED BLOOD CELLS
⢠Red blood cells are the most common type of
blood cell and the principal means of delivering
oxygen from the lungs to body tissues
⢠Red blood cells are also known as RBCs or
erythrocytes (from Greek erythros for "red" and
kytos for "hollow", with cyte translated as "cell").
Dr Alamzeb MBBS M.Phil 35
38. ⢠The red color of erythrocytes is due to the
heme group of hemoglobin.
⢠The blood plasma is straw-colored alone,
but the red blood cells change colors due
to the state of the hemoglobin:
⢠when combined with oxygen the resulting
oxyhemoglobin is scarlet
⢠and when oxygen has been released, the
resulting deoxyhemoglobin is darker,
appearing bluish through the blood vessel
walls.
Dr Alamzeb MBBS M.Phil 38
39. ⢠Erythrocytes in mammals are anucleate when
mature, meaning that they don't have a cell
nucleus and thus no DNA.
⢠In comparison, the erythrocytes of nearly all
other vertebrates have nuclei; the only known
exception is salamanders .
⢠Mammalian erythrocytes also lose their other
organelles including their mitochondria and
produce energy by fermentation, via glycolysis of
glucose followed by lactic acid production.
Dr Alamzeb MBBS M.Phil 39
40. ROUL EAUX FORMATION
⢠In large blood vessels, red blood cells
sometimes occur as a stack
⢠flat side next to flat side. This is known as
rouleaux formation,
⢠it occurs more often if the levels of certain
serum proteins are elevated, as for
instance during inflammation.
RED BLOOD CELLS
40
42. Concentration of Red Blood Cells in
the Blood
⢠Normal value Male
52,00000
Or 5.2 million per cubic
millimeter
⢠Normal value Female
47,00000
Or 4.7 million per cubic
millimeter
Âą 300000
40 to 45 % of the blood
volume
Dr Alamzeb MBBS M.Phil
One drop of blood = 1cmm 42
43. Shape of RBCs
Mammalian erythrocytes are
biconcave disks: flattened and
depressed in the center,
Dr Alamzeb MBBS M.Phil
43
44. Size of RBCs
⢠RBCs having a mean diameter of
approximately 8 microns
Dr Alamzeb MBBS M.Phil
44
46. Size at thin point
1 micron at thinnest point
The average volume of the red blood cell is 90 to 95 cubic micrometers.
Dr Alamzeb
46
Dr Alamzeb MBBS M.Phil
48. Thickness continue
A sheet of paper is approximately 75 micron thick
Therefore 10 Erythrocytes could be aligned side
by side across the edge of a sheet paper
Dr Alamzeb MBBS M.Phil
48
49. Shape of RBCs Under Microscope
Red blood cells (erythrocytes) shown above
in a stained slide. Note how they stain darker
at the edges than in the middle reflecting
their biconcave shape. Dr Alamzeb MBBS M Phil
49
50. Appearance under microscope
Red blood cells (erythrocytes) shown in a stained slide.
Note how they stain darker at the edges than in the
middle reflecting their biconcave shape.
50
51. Concentration of Red Blood Cells in the Blood
⢠In normal men, the average number of red
blood cells per cubic millimeter is
5,200,000 (Âą300,000);
⢠in normal women, it is 4,700,000
(Âą300,000).
⢠Persons living at high altitudes have
greater numbers of red blood cells.
Dr Alamzeb MBBS M.Phil
51
52. Quantity of Hemoglobin in the Cells.
⢠Red blood cells have the ability to concentrate
hemoglobin in the cell fluid up to about 34 grams in each
100 milliliters of cells.
⢠The concentration does not rise above this value,
because this is the metabolic limit of the cell's
hemoglobin-forming mechanism.
⢠Furthermore, in normal people, the percentage of
hemoglobin is almost always near the maximum in each
cell.
⢠However, when hemoglobin formation is deficient, the
percentage of hemoglobin in the cells may fall
considerably below this value, and the volume of the red
cell may also decrease because of diminished
hemoglobin to fill the cell.
52
53. ⢠When the hematocrit (the percentage of
blood that is cells-normally, 40 to 45 per
cent) and the quantity of hemoglobin in
each respective cell are normal, the whole
blood of men contains an average of 15
grams of hemoglobin per 100 milliliters of
blood;
⢠for women, it contains an average of 14
grams per 100 milliliters.
Dr Alamzeb MBBS M.Phil
53
54. oxygen carrying capacity
⢠Each gram of pure hemoglobin is capable
of combining with 1.34 milliliters of
oxygen.
⢠Therefore, in a normal man, a maximum
of about 1.34*15 = 20 milliliters of oxygen
can be carried in combination with
hemoglobin in each 100 milliliters of blood,
⢠And in a normal woman,1.3*14 = 19
milliliters of oxygen can be carried. MBBS M.Phil
Dr Alamzeb
54
55. Total surface area
The total surface area of
the RBCs is about
3800 square meters,
2000 time greater than
the total body surface
55
Dr Alamzeb MBBS M.Phil
56. Characteristic
⢠The shape of RBCs can change
remarkably as the cells pass through
capillaries.
⢠Actually RBC is like such a BAG that can
be deformed into almost any shape
⢠The cell has great excess of cell
membrane for the quantity of material in
side, deformities does not rupture the
membrane
Dr Alamzeb MBBS M.Phil
56
57. Change of shape
As you can see by the above photomicrograph red blood cells in
life are highly deformable and are able to squeeze through 57
59. Life History Of Erythrocytes
⢠Under normal condition 2.5
million erythrocytes are
destroyed every second
⢠This amount seems staggering
loss of RBCs
⢠Until it is realized that the loss
represent only 0.00001% of the
total 25 trillion RBCs contained
in normal adult circulation
⢠Further more those 2.5 million
RBCs are replaced by the
production of an equal number
of RBCs every second
Dr Alamzeb MBBS M.Phil 59
60. Life span
⢠The RBCs lack a nucleus so
it has no power of repair &
reproduction.
⢠It days are strictly numbered
⢠Average life span is 120
days
⢠It has been calculated that
each RBC travels 175 miles
in the course its
comparatively short life
Dr Alamzeb MBBS M.Phil 60
63. Haematopoiesis
⢠Haematopoiesis is an active process
which maintain normal number of
circulating blood cell & respond rapidly to
increased demands such as bleeding or
infection
63
Dr Alamzeb MBBS M.Phil
64. Erythropoiesis
⢠Erythropoiesis is an active process which
maintain normal number of circulating red
blood cell & respond rapidly to increased
demands such as bleeding or hypoxia
64
65. Areas of the Body That Produce Red Blood Cells.
⢠In the early weeks of
embryonic life, primitive,
nucleated red blood cells are
produced in the yolk sac.
⢠During the middle trimester of
gestation, the liver is the main
organ for production of red
blood cells, but reasonable
numbers are also produced in
the spleen and lymph nodes.
⢠Then, during the last month or
so of gestation and after birth,
red blood cells are produced
exclusively in the bone
marrow.
65
Dr Alamzeb MBBS M.Phil
66. Produce of Red Blood Cells by bone marrow.
⢠The bone marrow of
essentially all bones
produces red blood cells until
a person is 5 years old.
⢠The marrow of the long
bones, except for the
proximal portions of the
humeri and tibiae, becomes
quite fatty and produces no
more red blood cells after
about age 20 years.
⢠Beyond this age, most red
cells continue to be produced
in the marrow of the â˘Even in these
membranous bones, such as bones, the
marrow becomes
the vertebrae, sternum, ribs, less productive as
and ilia. age increases.
66
67. ⢠Bone marrow that actively produces blood
cells is called red marrow, and bone
marrow that no longer produces blood
cells is called yellow marrow.
Dr Alamzeb MBBS M.Phil
67
68. Pluripotential Hematopoietic stem cell
ď§ All blood cells (RBCs, WBCs
and platelets) in the bone
marrow come from the same
type of cell, called the
ď§ pluripotential
hematopoietic stem
cell
ď§ This group of cells has
the potential to form any of
the different types of blood
cells and also to reproduce
itself.
ď§ As these cells reproduce, a
small portion of them
remains exactly like the
original pluripotential cells
and is retained in the bone 68
marrow to maintain a supply Dr Alamzeb MBBS M.Phil
69. Committed stem cells
ď§ The different committed
stem cells, when grown in
culture, will produce
colonies of specific types
of blood cells.
ď§ A committed stem cell that
produces erythrocytes is
called a colony-forming
unit-erythrocyte, and the
abbreviation CFU-E is
used to designate this
type of stem cell.
ď§ Likewise, colony-forming
units that form
granulocytes and
monocytes have the
designation CFU-GM, and
so forth. 69
71. Growth inducers
⢠Growth and reproduction of the different stem
cells are controlled by multiple proteins called
growth inducers.
⢠Four major growth inducers have been
described.
⢠One of these, interleukin-3, promotes growth
and reproduction of virtually all the different
types of committed stem cells,
⢠whereas the others induce growth of only
specific types of cells.
71
72. Differentiation Inducers.
⢠The growth inducers
promote growth but
not differentiation of
the cells. This is the
function of another
set of proteins called
differentiation
inducers.
⢠Each of these causes
one type of committed
stem cell to
differentiate one or 72
73. ⢠Formation of the growth inducers and differentiation
inducers is itself controlled by factors outside the
bone marrow.
⢠For instance, in the case of erythrocytes (red blood
cells), exposure of the blood to low oxygen for a long
time results in growth induction, differentiation, and
production of greatly increased numbers of
erythrocytes
⢠In the case of some of the white blood cells,
infectious diseases cause growth, differentiation, and
eventual formation of specific types of white blood
cells that are needed to combat each infection.
73
74. Stages of Differentiation of Red Blood Cells
⢠The first cell that
can be identified
as belonging to
the red blood cell
series is the
proerythroblast,
⢠Under appropriate
stimulation, large
numbers of these
cells are formed
from the CFU-E
stem cells.
74
75. ⢠Once the proerythroblast has been formed, it divides
multiple times, eventually forming many mature red
blood cells. The first-generation cells are called
basophil erythroblasts
⢠because they stain with basic dyes; the cell at this
time has accumulated very little hemoglobin.
⢠In the succeeding generations, the cells become
filled with hemoglobin to a concentration of about 34
per cent, the nucleus condenses to a small size, and
its final remnant is absorbed or extruded from the
cell.
⢠At the same time, the endoplasmic reticulum is also
reabsorbed. The cell at this stage is called a
reticulocyte because it still contains a small amount
of basophilic material, consisting of remnants of the
Golgi apparatus, mitochondria, and a few other
cytoplasmic organelles.
⢠During this reticulocyte stage, the cells pass from
the bone marrow into the blood capillaries by
diapedesis (squeezing through the pores of the
capillary membrane).
75
76. ⢠The remaining basophilic material in the
reticulocyte normally disappears within 1
to 2 days, and the cell is then a mature
erythrocyte.
76
77. ⢠The proliferation & differentiation of stem
cells are under the control of growth
factors produced by several cells including
stromal cells & lymphocytes.
⢠These growth factors binds to specific
receptors on the cell surface , promote
proliferation,differention ,survival &
functions of mature cells
Dr Alamzeb MBBS M.Phil
77
78. Regulation of Red Blood Cell Production-Role of Erythropoietin
⢠The total mass of red blood cells in the
circulatory system is regulated within
narrow limits, so that
⢠(1) an adequate number of red cells is
always available to provide sufficient
transport of oxygen from the lungs to the
tissues, yet
⢠(2) the cells do not become so numerous
that they impede blood flow.
78
79. Tissue Oxygenation Is the Most Essential
Regulator of Red Blood Cell Production.
⢠Any condition that causes the quantity of oxygen
transported to the tissues to decrease ordinarily
increases the rate of red blood cell production.
⢠Thus, when a person becomes extremely anemic as a
result of hemorrhage or any other condition, the bone
marrow immediately begins to produce large
quantities of red blood cells.
⢠Also, destruction of major portions of the bone marrow
by any means, especially by x-ray therapy, causes
hyperplasia of the remaining bone marrow, thereby
attempting to supply the demand for red blood cells in
the body.
79
80. High Altitudes
⢠At very high altitudes, where the quantity of
oxygen in the air is greatly decreased,
insufficient oxygen is transported to the tissues,
and red cell production is greatly increased.
⢠In this case, it is not the concentration of red
blood cells in the blood that controls red cell
production but the amount of oxygen transported
to the tissues in relation to tissue demand for
oxygen.
80
81. Diseases
⢠Various diseases of the circulation that cause
decreased blood flow through the peripheral
vessels, and particularly those that cause failure
of oxygen absorption by the blood as it passes
through the lungs, can also increase the rate of
red cell production.
⢠This is especially apparent in prolonged cardiac
failure and in many lung diseases, because the
tissue hypoxia resulting from these conditions
increases red cell production, with a resultant
increase in hematocrit and usually total blood
volume as well.
81
83. ⢠A hormone called erythropoietin and low oxygen
levels regulate the production of RBCs.
⢠Any factor that decreases the oxygen level in the
body, such as lung disease or anemia (low number of
RBCs), increases the level of erythropoietin in the
body.
⢠Erythropoietin then stimulates production of RBCs by
stimulating the stem cells to produce more RBCs and
increasing how quickly they mature.
⢠Ninety percent of erythropoietin is made in the
kidneys. When both kidneys are removed, or when
kidney failure is present, that person becomes anemic
due to lack of erythropoietin.
⢠Iron,vitamin B-12 and folate are essential in the
production of RBCs.
Dr Alamzeb MBB M.Phil 83
86. ROLE OF VITAMIN B12 AND FLIC ACID IN MATURATION OF RBCs
⢠B12 & folic acid is important for final maturation of
RBCs.
⢠Both of these are essential for the synthesis DNA
⢠Because each in a different way is required for the
formation of thymidine triphosphate,one of the
essential building block of DNA.
⢠There fore lack of either B12 or folic acid cause
abnormal & diminished DNA & consequently, failure
of nuclear maturation & cell division.
⢠Furthermore the erythroblast fails to proliferate
rapidly & produce large red cells called Macrocytes,
has a flimsy & often irregular membrane
⢠the oxygen carrying capacity is normal but the life
span is reduced by one half to one third normal.
86
90. ⢠The primary function of red blood cells is to transport
oxygen from the lungs to all cells of the body.
⢠RBCs contain a protein called hemoglobin that
actually carries the oxygen.
⢠In the capillaries, the oxygen is released to be used by
the cells of the body.
⢠Ninety-seven percent of the oxygen that is carried by
the blood from the lungs is carried by hemoglobin; the
other three percent is dissolved in the plasma.
⢠Hemoglobin allows the blood to transport 30 to 100
times more oxygen than could be dissolved in the
plasma
â˘
⢠Alamzeb
MBBS M.Phil
90
91. ⢠Hemoglobin combines loosely with oxygen in
the lungs, where the oxygen level is high, and
then easily releases it in the capillaries, where
the oxygen level is low.
⢠Each molecule of hemoglobin contains four
iron atoms,
⢠and each iron atom can bind with one
molecule of oxygen (which contains two oxygen
atoms, called O2)
⢠for a total of four oxygen molecules (4 *O 2) or
eight atoms of oxygen for each molecule of
hemoglobin.
⢠The iron in hemoglobin gives blood its red 91
92. ⢠Carbon dioxide is formed in the cells as a
byproduct of many chemical reactions.
⢠It enters the blood in the capillaries and is
brought back to the lungs and released there
and then exhaled as we breathe.
⢠RBCs contain an enzyme called carbonic
anhydrase which helps the reaction of carbon
dioxide (CO2) and water (H2O) to occur 5,000
times faster.
⢠Carbonic acid is formed, which then separates
into hydrogen ions and bicarbonate ions:
92
93. Chemical reaction
Carbonic Anhydrase
CO2 + H2O H2CO3 H+ + HCO3-
carbon dioxide + water carbonic acid + hydrogen ion + bicarbonate ion
Alamzeb MBBS M.Phil
93
94. ⢠The hydrogen ions then combine with
hemoglobin
⢠and the bicarbonate ions go into the plasma.
⢠Seventy percent of the CO2 is removed in this
way.
⢠Seven percent of the CO2 is dissolved in the
plasma.
⢠The remaining 23 percent of the CO 2 combines
directly with hemoglobin and then is released
into the lungs.
Alamzeb MBBS M.Phil
94
95. OTHER FUNCTIONS BESIDES TRANSPORT OF HEMOGLOBIN.
⢠The red blood cells contain a large quantity of
carbonic anhydrase, an enzyme that catalyzes the
reversible reaction between carbon dioxide (CO2)
and water to form carbonic acid (H2CO3), increasing
the rate of this reaction several thousand
fold.H2o+Co2 H2Co3
⢠The rapidity of this reaction makes it possible for the
water of the blood to transport enormous quantities
of CO2 in the form of bicarbonate ion (HCO3-) from the
tissues to the lungs,
⢠where it is reconverted to CO2 and expelled into the
atmosphere as a body waste product.
⢠The hemoglobin in the cells is an excellent acid-base
buffer (as is true of most proteins), so that the red
blood cells are responsible for most of the acid-base
buffering power of whole blood. 95
10 or 11 depending on whether muscles and skeleton are considered one system. Also: Lymphatic system is anatomical system, physiologically it belongs to circulatory, digestive and immune systems. Regulation of plasma concentration: The endocrine system acts on bones, kidneys, and intestine to ensure that plasma calcium concentrations remain within a certain range.