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•Welcome in the beautiful valley of swat




                                           2
3
Welcome in the beautiful valley of swat




                                          4
5
And also in SMC




Saidu Medical College




                                          6
Facts about him
•   Believe in hard work
•   Punctuality
•   Discipline
•   No illegal approach




                               7
8
9
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
Review Levels of Organization




                                11
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
Organ - Systems


Operate as integrated
        units




                            13
Function and Process:



What is purpose or function?




                               14
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
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
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
Dr Alamzeb MBBS M.Phil

                   18
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
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
A speck of blood (1 cu mm)




                             21
A speck of blood (1 cu mm) the size of
this    contains 5 million RBCs, 300,000
platelets, and 7,000 white blood cells.




                          Dr Alamzeb MBBS M.Phil   22
Blood is the most commonly tested
part of the body,
Screening,

Diagnosis

& prognosis of diseases

                          Dr Alamzeb MBBS M.Phil

                                            23
Easily accessible




                    24
Easily obtainable




              Dr Alamzeb MBBS M.Phil 25
Easily testable




           Dr Alamzeb MBBS M.Phil   26
• It is truly the river of
  life.
Every cell in the body gets
its



                              27
28
If we take some blood, prevented from clotting, in a

centrifuge, after centrifugation we have this result.




                                                        29
Let us understand the composition of the sedimented blood:




                                                             30
Composition of Blood
                Blood consist of
                   1 Red cell
                   2 White cell
                   3 Platelets
                   4 Plasma –
 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
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
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
RBCs




       Dr Alamzeb MBBS M.Phil
                        34
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
Dr Alamzeb MBBS M.Phil
                  36
RED BLOOD CELLS




                                  37
                  Dr Alamzeb MBBS M.Phil
• 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
• 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
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
Dr Alamzeb MBBS M.Phil   RED BLOOD CELLS
                                     41
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
Shape of RBCs
Mammalian erythrocytes are
 biconcave disks: flattened and
 depressed in the center,




                                  Dr Alamzeb MBBS M.Phil
                                                    43
Size of RBCs
• RBCs having a mean diameter of
  approximately 8 microns




                              Dr Alamzeb MBBS M.Phil
                                                       44
Thickness
2 microns at thickest point




                    Dr Alamzeb MBBS M.Phil   45
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
47
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
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
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
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
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
• 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
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
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
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
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
Dr Alamzeb MBBS M.Phil
                         58
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
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
61
Dr Alamzeb MBBS M.Phil
                   62
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
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
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
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              •Even in these
  membranous bones, such as         bones, the
                                    marrow becomes
  the vertebrae, sternum, ribs,     less productive as
  and ilia.                         age increases.
                                                     66
• 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
Pluripotential Hematopoietic stem cell
 All blood cells (RBCs, WBCs
  and platelets) in the bone
  marrow come from the same
  type of cell, called the

 pluripotential
  hematopoietic stem
  cell
 This group of cells has
  the potential to form any of
  the different types of blood
  cells and also to reproduce
  itself.
 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
Committed stem cells
 The different committed
  stem cells, when grown in
  culture, will produce
  colonies of specific types
  of blood cells.
 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.
 Likewise, colony-forming
  units that form
  granulocytes and
  monocytes have the
  designation CFU-GM, and
  so forth.                    69
70
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
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
• 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
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
•   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
• The remaining basophilic material in the
  reticulocyte normally disappears within 1
  to 2 days, and the cell is then a mature
  erythrocyte.




                                              76
• 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
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
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
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
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
Erythropoietin

                 82
• 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
Hypoxia                  Erythropoietin         RBCs production

                        Hemopoietic stem cells
kidney

                          Proerythroblasts
 Erythropoietin
                          Red blood cells
  Increase                Tssue oxygenation

                              Decrease

              factors that decrease tissue oxygenation
                1 Low blood volume
                2 anemia
                3 low hemoglobin
                4 poor blood flow
                  5 pulmonary disease
                  6 cardiac disease
                  8 hemorrhage
                                                                     84
                                                      Dr Alamzeb MBB M.Phil
85
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
Hemoglobine break down




                         87
     Dr Alamzeb MBBS M.Phil
S
U
M
M
E
R
Y
    Alamzeb MBBS M.Phil

                          88
Dr Alamzeb MBBS M.Phil
                89
• 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
•
           •                                    Alamzeb
               MBBS M.Phil
                                                      90
• 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
• 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
Chemical reaction

                         Carbonic Anhydrase

         CO2 + H2O                  H2CO3       H+ + HCO3-


carbon dioxide + water         carbonic acid + hydrogen ion + bicarbonate ion




                                                          Alamzeb MBBS M.Phil
                                                                        93
• 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
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
96
97
98
99

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Physiology of Blood Cells and Functions in Homeostasis

  • 1. 1
  • 2. •Welcome in the beautiful valley of swat 2
  • 3. 3
  • 4. Welcome in the beautiful valley of swat 4
  • 5. 5
  • 6. And also in SMC Saidu Medical College 6
  • 7. Facts about him • Believe in hard work • Punctuality • Discipline • No illegal approach 7
  • 8. 8
  • 9. 9
  • 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
  • 11. Review Levels of Organization 11
  • 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
  • 13. Organ - Systems Operate as integrated units 13
  • 14. Function and Process: What is purpose or function? 14
  • 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
  • 18. Dr Alamzeb MBBS M.Phil 18
  • 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
  • 21. A speck of blood (1 cu mm) 21
  • 22. A speck of blood (1 cu mm) the size of this contains 5 million RBCs, 300,000 platelets, and 7,000 white blood cells. Dr Alamzeb MBBS M.Phil 22
  • 23. Blood is the most commonly tested part of the body, Screening, Diagnosis & prognosis of diseases Dr Alamzeb MBBS M.Phil 23
  • 25. Easily obtainable Dr Alamzeb MBBS M.Phil 25
  • 26. Easily testable Dr Alamzeb MBBS M.Phil 26
  • 27. • It is truly the river of life. Every cell in the body gets its 27
  • 28. 28
  • 29. If we take some blood, prevented from clotting, in a centrifuge, after centrifugation we have this result. 29
  • 30. Let us understand the composition of the sedimented blood: 30
  • 31. Composition of Blood Blood consist of 1 Red cell 2 White cell 3 Platelets 4 Plasma – 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
  • 34. RBCs Dr Alamzeb MBBS M.Phil 34
  • 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
  • 36. Dr Alamzeb MBBS M.Phil 36
  • 37. RED BLOOD CELLS 37 Dr Alamzeb MBBS M.Phil
  • 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
  • 41. Dr Alamzeb MBBS M.Phil RED BLOOD CELLS 41
  • 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
  • 45. Thickness 2 microns at thickest point Dr Alamzeb MBBS M.Phil 45
  • 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
  • 47. 47
  • 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
  • 58. Dr Alamzeb MBBS M.Phil 58
  • 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
  • 61. 61
  • 62. Dr Alamzeb MBBS M.Phil 62
  • 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 •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  All blood cells (RBCs, WBCs and platelets) in the bone marrow come from the same type of cell, called the  pluripotential hematopoietic stem cell  This group of cells has the potential to form any of the different types of blood cells and also to reproduce itself.  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  The different committed stem cells, when grown in culture, will produce colonies of specific types of blood cells.  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.  Likewise, colony-forming units that form granulocytes and monocytes have the designation CFU-GM, and so forth. 69
  • 70. 70
  • 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
  • 84. Hypoxia Erythropoietin RBCs production Hemopoietic stem cells kidney Proerythroblasts Erythropoietin Red blood cells Increase Tssue oxygenation Decrease factors that decrease tissue oxygenation 1 Low blood volume 2 anemia 3 low hemoglobin 4 poor blood flow 5 pulmonary disease 6 cardiac disease 8 hemorrhage 84 Dr Alamzeb MBB M.Phil
  • 85. 85
  • 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
  • 87. Hemoglobine break down 87 Dr Alamzeb MBBS M.Phil
  • 88. S U M M E R Y Alamzeb MBBS M.Phil 88
  • 89. Dr Alamzeb MBBS M.Phil 89
  • 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 • • 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
  • 96. 96
  • 97. 97
  • 98. 98
  • 99. 99

Editor's Notes

  1. 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.