1 Blood Physiology By Dr. Abdulhalim Serafi, MB ChB, MSc, PhD, FESC Assistant Professor & Consultant Cardiologist Faculty of Medicine Umm Al-Qura University.

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Blood PhysiologyBlood Physiology

By

Dr. Abdulhalim Serafi, MB ChB, MSc, PhD, FESCDr. Abdulhalim Serafi, MB ChB, MSc, PhD, FESC Assistant Professor & Consultant CardiologistAssistant Professor & Consultant Cardiologist

Faculty of MedicineFaculty of Medicine Umm Al-Qura UniversityUmm Al-Qura University

Makkah Al-MukarramahMakkah Al-Mukarramah

Drserafi.comDrserafi.com

Serafi @uqu.edu.saSerafi @uqu.edu.sa

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Major Components of the Major Components of the Circulatory SystemCirculatory System

Heart

Blood vessels

Blood

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Composition of BloodComposition of BloodBlood is a specialized connective tissue made of cells or (corpuscles) suspended in a clear yellowish fluid called the plasma.

  (A (Cellular elements: (formed elements, or cells, or corpuscles):The cellular elements constitute 40 –45% of the total blood volume and are of 3 types:erythrocytes = RBCs (>95%) .leukocytes = WBCs .

thrombocytes = platelets (cell fragments).

   )B (Plasma:

The plasma constitutes 55-60% of the total blood volume, and it consists of water (90%) and dissolved solutes (10%).

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The cellular elements constitute 40 –45% of the total blood volume and are of 3 types:

a. Red blood cells = red blood corpuscles (RBC) or erythrocytes: mature red blood cells lack nuclei and all sub-cellular organelles. Normally, there are about 5 million RBCs per mm3. When they are decreased the condition is called anemia and when increased, it is called polycythemia.

b. White blood cells (WBC) or leucocytes or leukocytes: Normally, there are 4000 to 11000 WBCs per mm3. When they are decreased the condition is called leucopenia and when increased, it is called leucocytosis.

c. Thrombocytes or blood platelets - Normally, there are 300000 platelets per mm3. When they are decreased the condition is called thrombocytopenia and when increased, it is called thrombocytosis.

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Formed Elements of BloodFormed Elements of BloodRed blood cells (erythrocytes)

White blood cells (leukocytes)granular leukocytesneutrophils

eosinophils

basophils

agranular leukocyteslymphocytes = T cells, B cells, and natural killer cells

monocytes

Platelets (special cell fragments)

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PlasmaPlasma

The plasma constitutes 55-60% of the total blood volume, The plasma constitutes 55-60% of the total blood volume, and it consists of water (90%) and dissolved solutes and it consists of water (90%) and dissolved solutes (10%). The later include(10%). The later include::

a. Organic substances: plasma proteins (7.1%), lipids, a. Organic substances: plasma proteins (7.1%), lipids, hormones, enzymes and nutrients and waste products hormones, enzymes and nutrients and waste products

(2%)(2%)..((

b. Inorganic substances (0.9%) which include the various b. Inorganic substances (0.9%) which include the various electrolytes e.g. Naelectrolytes e.g. Na++, Cl, Cl--, HCO, HCO

33--, Ca, Ca++++, PO, PO

44--, etc, etc..

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Components of BloodComponents of Blood

HematocritHematocrit55%55% plasmaplasma

45%45% cellscells 99%99% RBCsRBCs

> >1%1% WBCs and plateletsWBCs and platelets

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Physical Properties of BloodPhysical Properties of Blood 1 .Volume = 7-9% of body weight :

5-6 L in adult males.

4-5 L in adult females.

2 .Temperature ~ 100.4 oF (38 oC).

33 . .The color of blood is red – due to HbThe color of blood is red – due to Hb..

44 . .Blood is opaque due to cellular elements, particularly the RBCs. So, Blood is opaque due to cellular elements, particularly the RBCs. So, after hemolysis blood becomes transparentafter hemolysis blood becomes transparent..

55 . .The pH of arterial blood is 7.4 ( venous blood has a slightly lower pH)The pH of arterial blood is 7.4 ( venous blood has a slightly lower pH)..

66..Viscosity – blood is about 5 times as viscous as water because of cells and Viscosity – blood is about 5 times as viscous as water because of cells and plasma proteins (plasma’s viscosity is 2 times that of water). Blood plasma proteins (plasma’s viscosity is 2 times that of water). Blood viscosity is important in maintaining arterial blood pressureviscosity is important in maintaining arterial blood pressure

77 . .The net effective colloid pressure of the plasma is 25 mm Hg and is The net effective colloid pressure of the plasma is 25 mm Hg and is known as the oncotic pressureknown as the oncotic pressure

. .88 . .Osmolarity of the plasma – 290-300 mosmoles/LOsmolarity of the plasma – 290-300 mosmoles/L

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OsmolarityOsmolarityNaCl solution of molarity equal to 150 mmol/L has an osmolarity of 300 NaCl solution of molarity equal to 150 mmol/L has an osmolarity of 300 mosmoles/L because of disassociation to Namosmoles/L because of disassociation to Na++ and Cl. The and Cl. The osmolarities of glucose solutions are equal to their corresponding osmolarities of glucose solutions are equal to their corresponding molaritiesmolarities..

  Osmolality of the plasma is 290 – 300 mosmoles/LOsmolality of the plasma is 290 – 300 mosmoles/L..

  Iso-osmotic solutions are solutions with the same osmolarity as plasma Iso-osmotic solutions are solutions with the same osmolarity as plasma (e.g. 0.9 % NaCl solution, i.e., 0.9 g of NaCl dissolved in 100 mL of (e.g. 0.9 % NaCl solution, i.e., 0.9 g of NaCl dissolved in 100 mL of water or 9 g of NaCl dissolved in 1 L of water, has an osmolarity of water or 9 g of NaCl dissolved in 1 L of water, has an osmolarity of about 300 mosmoles/Labout 300 mosmoles/L..

  Hypo-osmotic solutions are solutions with a lower osmolarity than Hypo-osmotic solutions are solutions with a lower osmolarity than plasmaplasma..

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Major Functions of the BloodMajor Functions of the Blood11 . .Nutrition (by transporting the absorbed food from the GIT to the Nutrition (by transporting the absorbed food from the GIT to the

tissues)tissues)..22 . .RespirationRespiration..

33 . .Excretion (by transporting the waste products from the tissues to Excretion (by transporting the waste products from the tissues to the excretory organs e.g. urea and creatinine to the kidneys)the excretory organs e.g. urea and creatinine to the kidneys)..

44 . .Regulation of metabolism (by transporting hormones from Regulation of metabolism (by transporting hormones from various endocrine glands to the tissue and also by regulating various endocrine glands to the tissue and also by regulating their secretion)their secretion)..

55 . .Regulation of the body temperatureRegulation of the body temperature..66 . .Marinating the acid-base balanceMarinating the acid-base balance..

77 . .Regulation of water balanceRegulation of water balance.. 88 . .Blood clottingBlood clotting..

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Plasma ProteinsPlasma ProteinsThe amount of the plasma proteins averages 7 gm% (6-8 gm%) The amount of the plasma proteins averages 7 gm% (6-8 gm%) which are divided as followswhich are divided as follows::

  Albumin – 4g/100mlAlbumin – 4g/100ml..Globulins – 2.7g/100ml (Globulins – 2.7g/100ml (1, 1, 2, 2, 1, 1, 2)2)..Fibrinogen – 0.3g/100mlFibrinogen – 0.3g/100ml..In addition to small amounts of other proteins (e.g. certain In addition to small amounts of other proteins (e.g. certain hormones, prothrombin and most of the other clotting factors)hormones, prothrombin and most of the other clotting factors)..

  Site of Plasma Protein SynthesisSite of Plasma Protein Synthesis::

All plasma proteins are formed in the liver except the gamma All plasma proteins are formed in the liver except the gamma globulins which are formed by plasma cellsglobulins which are formed by plasma cells..

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A/G RatioA/G Ratio

Normally, this ratio is 1.2Normally, this ratio is 1.2

The determination of the A/G ratio is important clinically; The determination of the A/G ratio is important clinically; it can be used as a liver function testit can be used as a liver function test..

It is increased in cases of congenital agammaglobulineimaIt is increased in cases of congenital agammaglobulineima..

It is decreased in cases of advanced liver diseases and It is decreased in cases of advanced liver diseases and severe infectionssevere infections..

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Functions of Plasma ProteinsFunctions of Plasma Proteins 11 . .The effective osmotic pressure in the vascular system is The effective osmotic pressure in the vascular system is

produced 70-80% by albumin because of its greater produced 70-80% by albumin because of its greater amountamount

22 . .Defense (immunity)Defense (immunity)..33 . .Haemostatic function (blood clotting)Haemostatic function (blood clotting)..

44 . .They share in the production of blood viscosityThey share in the production of blood viscosity..55 . .They produce up to 15% of the buffering power of the They produce up to 15% of the buffering power of the

bloodblood66 . .Plasma proteins combine loosely with many substances, Plasma proteins combine loosely with many substances,

including hormones. This prevents rapid diffusion of these including hormones. This prevents rapid diffusion of these substances in the tissue spaces or their rapid loss in urinesubstances in the tissue spaces or their rapid loss in urine..

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Characteristics of ErythrocytesCharacteristics of Erythrocytes

* *Small, biconcave disk discs with an average Small, biconcave disk discs with an average diameter of ~ 7.5 micronsdiameter of ~ 7.5 microns..

* *Non-nucleatedNon-nucleated..

* *No ribosomesNo ribosomes..

* *No mitochondriaNo mitochondria.. * *What type of ATP synthesis can they doWhat type of ATP synthesis can they do??

* *Life span ~ 120 days (or less)Life span ~ 120 days (or less)..

* *Normal count averages 5 million/cubic mmNormal count averages 5 million/cubic mm..

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Physiological Factors Affecting Physiological Factors Affecting Red Cell CountRed Cell Count

      *Age: it is high in newly born infants and low in old Age: it is high in newly born infants and low in old individualsindividuals

            * *Sex: it s higher in males than in females for two Sex: it s higher in males than in females for two

reasonsreasons:: a. androgens stimulate the production of RBCa. androgens stimulate the production of RBC

b. women lose blood via menstrationb. women lose blood via menstration

* *High altitudeHigh altitude

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Structure of RBCStructure of RBC

The red blood cells is formed of a mass of cytoplasm The red blood cells is formed of a mass of cytoplasm enclosed by plasma or a cell membraneenclosed by plasma or a cell membrane..

The cytoplasm is formed mostly of hemoglobin (Hb). The cytoplasm is formed mostly of hemoglobin (Hb). Each red blood cell contains about 30 picograms of Each red blood cell contains about 30 picograms of Hb. It also contains electrolytes and several Hb. It also contains electrolytes and several enzymesenzymes..

The plasma membrane contains glycoproteins and The plasma membrane contains glycoproteins and glycolipids. The biconcave shape of the red blood glycolipids. The biconcave shape of the red blood cells is produced by ankyrin and spectrincells is produced by ankyrin and spectrin..

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Normal, RBC's. Normal, RBC's. They have a They have a zone of central zone of central pallor about pallor about 1/3 the size of 1/3 the size of the RBC.). A the RBC.). A few small fuzzy few small fuzzy blue platelets blue platelets are seen. In the are seen. In the center of the center of the field are a field are a band band neutrophil on neutrophil on the left and a the left and a segmented segmented neutrophil on neutrophil on the rightthe right..

Normal Blood FilmNormal Blood Film::

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Functions of the RBCsFunctions of the RBCs

Transport of the respiratory gasesTransport of the respiratory gases

Play an important role in producing blood Play an important role in producing blood viscosityviscosity

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Factors affecting RBCS formation Factors affecting RBCS formation (erythropoiesis)(erythropoiesis)

11 . .The bone marrow: A healthy bone marrow is essential for The bone marrow: A healthy bone marrow is essential for normal hemopoiesisnormal hemopoiesis..

22 . .Diet: The followings must be sufficiently supplied for adequate Diet: The followings must be sufficiently supplied for adequate erythropoiesiserythropoiesis::

        Proteins of high biological valuesProteins of high biological values,,                   IronIron,,

                  Other minerals especially copper and cobaltOther minerals especially copper and cobalt,,

                All vitamins particularly vitamin BAll vitamins particularly vitamin B1212 and folic acid and folic acid

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33 . .Blood OBlood O22 tension: Erythropoiesis is inhibited when the tension: Erythropoiesis is inhibited when the

blood Oblood O22 tension increases and stimulated when it is tension increases and stimulated when it is

decreased (e.g. at high altitude and in lung diseases)decreased (e.g. at high altitude and in lung diseases)..

44 . .The kidneys: The kidneys secret erythropoietin, which The kidneys: The kidneys secret erythropoietin, which specifically simulate red blood cell formation in the specifically simulate red blood cell formation in the bone marrow. Obone marrow. O

22 lack stimulates erythropoiesis lack stimulates erythropoiesis indirectly through stimulating release of erythropoietinindirectly through stimulating release of erythropoietin..

55 . .The liver: It stores vitamin BThe liver: It stores vitamin B1212 and several minerals and several minerals

required red cell formation specially ironrequired red cell formation specially iron..

Factors affecting RBCS formation Factors affecting RBCS formation (erythropoiesis)(erythropoiesis)

24Normoblasts

Pronormoblast

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Osmotic fragility of the red blood cellsOsmotic fragility of the red blood cells

A 0.9% NaCl (saline) solution is isotonic with plasmaA 0.9% NaCl (saline) solution is isotonic with plasma..

When red cells are suspended in hypotonic saline, When red cells are suspended in hypotonic saline, water diffuses into the cells so they swell and may water diffuses into the cells so they swell and may rupture ( = hemolysis)rupture ( = hemolysis)..

The ability of the red blood cells to resist hemolysis in The ability of the red blood cells to resist hemolysis in hypotonic saline solutions determines their osmotic hypotonic saline solutions determines their osmotic fragilityfragility..

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Causes of hemolysisCauses of hemolysis .1 . .Incompatible (mismatched) blood transfusionIncompatible (mismatched) blood transfusion

22 . .Snake venom, certain bacterial toxins and some chemicals (e.g. Snake venom, certain bacterial toxins and some chemicals (e.g. arsenic)arsenic)..

33 . .Fat solvents e.g. etherFat solvents e.g. ether..44 . .Blood freezingBlood freezing..

55 . .Hereditary spherocytosisHereditary spherocytosis.. . .66 . .Abnormal HbAbnormal Hb

. .77 . .GDPD deficiencyGDPD deficiency . .88 . .Pyruvate kinase deficiencyPyruvate kinase deficiency

99 . .Abnormal immune rections that cause formation of red cell Abnormal immune rections that cause formation of red cell antibodiesantibodies..

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Blood grouping and blood transfusionBlood grouping and blood transfusion The outer layers of the red blood cell membranes The outer layers of the red blood cell membranes contain certain antigens, which are called contain certain antigens, which are called agglutinogens. They are chemically glycoproteins and agglutinogens. They are chemically glycoproteins and glycolipids. There are two types of such antigens glycolipids. There are two types of such antigens called A & B agglutinogens, and according to the called A & B agglutinogens, and according to the present type, the human blood is divided into the present type, the human blood is divided into the following 4 types or groupsfollowing 4 types or groups::

  11 . .Group A (42%) when only type A is presentGroup A (42%) when only type A is present

22 . .Group B (9%) when only type B is presentGroup B (9%) when only type B is present33 . .Group AB (3%) when both types A and B are presentGroup AB (3%) when both types A and B are present44 . .Group O (46%) when both types A and B are absentGroup O (46%) when both types A and B are absent

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The plasma contains certain gamma globulins called agglutinins, The plasma contains certain gamma globulins called agglutinins, which are antibodies to the red blood cell agglutinogens. These which are antibodies to the red blood cell agglutinogens. These antibodies are of two types: anti-A and anti-B agglutinins. At antibodies are of two types: anti-A and anti-B agglutinins. At birth, the quantity of agglutinins is almost zero. However, they birth, the quantity of agglutinins is almost zero. However, they begin to be produced within a few months after birth. Infants begin to be produced within a few months after birth. Infants develop agglutinins against the agglutinigens not present in develop agglutinins against the agglutinigens not present in their own red blood cells. Thustheir own red blood cells. Thus,,

Type A subjects develop anti-B agglutininsType A subjects develop anti-B agglutinins Type B subjects develop anti-A agglutininsType B subjects develop anti-A agglutinins

Type AB subjects develop neitherType AB subjects develop neither Type O subjects develop bothType O subjects develop both

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Therefore, agglutinogens normally never exist Therefore, agglutinogens normally never exist with their corresponding agglutinins, otherwisewith their corresponding agglutinins, otherwise An antigen-antibody reaction would occur that An antigen-antibody reaction would occur that leads to the dangerous process or red cell leads to the dangerous process or red cell

agglutinationagglutination..

This occurs in cases of mismatched blood This occurs in cases of mismatched blood transfusiontransfusion..

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Blood Groups and Blood TypesBlood Groups and Blood Types

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The Rh antigen (factor)The Rh antigen (factor)This is the agglutinogen normally present in the red blood cells of This is the agglutinogen normally present in the red blood cells of Rhesus monkeys (hence the name Rh). There are 6 varieties Rhesus monkeys (hence the name Rh). There are 6 varieties known as the C, D, E, c, d, e antigens. These antigens were also known as the C, D, E, c, d, e antigens. These antigens were also discovered in the human red blood cells, particularly the D and discovered in the human red blood cells, particularly the D and d antigens and D has the strongest antigenic effect. They are d antigens and D has the strongest antigenic effect. They are inherited from both the father and the mother, and D is inherited from both the father and the mother, and D is dominant while d is recessive, so that the genotypes DD and Dd dominant while d is recessive, so that the genotypes DD and Dd are Rh+ while genotype dd is Rhare Rh+ while genotype dd is Rh..

  The Rh agglutinins are not normally present but they are formed The Rh agglutinins are not normally present but they are formed in the plasma of Rh- persons only after exposure to Rh+ blood. in the plasma of Rh- persons only after exposure to Rh+ blood. The Rh agglutinins have a small size, so they can cross the The Rh agglutinins have a small size, so they can cross the placenta more easier than the other agglutininsplacenta more easier than the other agglutinins..

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ABO Blood TypingABO Blood Typing

• With ABO, person makes antibodies (agglutinens) against factors (agglutinogens) he/she does NOT have on his/her cells

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ABO Blood TypesABO Blood Types

[1] Universal Recipient [2] Universal Donor

Blood Type A B AB[1] O[2]

Agglutinogens (antigen) Present

A B A & B (neither)

Makes Agglutinins (antibodies)

AgainstB A (neither) A & B

May Receive Blood From:

A, O B, O A, B, AB, O O

May Give Blood To: A, AB B, AB AB A, B, AB, O

Genotype IAIA or IAi IBIB or IBi IAIB ii

Rh FactorPresent or

Absent(A+ or A-)

Present or Absent

(B+ or B-)

Present or Absent

(AB+ or AB-)

Present or Absent

(O+ or O-)

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Rh Blood TypesRh Blood Types

Blood Type Rh+ Rh-

Agglutinogen D (antigen proteins)

Present or AbsentPresent Absent

Makes Agglutinins (antibodies) Against Agglutinogen

No Yes[1]

May Receive Blood From: Rh+ or Rh- Rh-[2]

May Give Blood To Without Reaction[2]:

Rh+ Rh+ or Rh‑

Genotype DD or Dd dd

[1] Only makes antibodies (agglutinens) after exposure to Rh+ blood cells (via transfusion or during birth process)[2] Transfusion of Rh- individual with Rh+ blood results in production of anti-D agglutinens; sensitizes person to Rh factor and may result in anaphylaxis if exposed a second time. Erythroblastosis fetalis arises when Rh- mother has been exposed to Rh+ blood and is carrying Rh+ child.

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Importance of the Rh factorImportance of the Rh factor

Transfusion reactionsTransfusion reactions..11

22 . .Hemolytic disease of the new-borneHemolytic disease of the new-borne