THE BLOOD Presented By : Dr. Ullas Saxena, JR - 1Oral Medicine & Radiology
Blood is a specialized connective tissue containing intracellular fluid plasma and blood components – RBCs , WBCs and blood platelets.
An average 70 kg man has almost 5L blood (5.5 kg).
Blood circulates throughout the body and supports the functions of all other body tissues.
Blood integrates tissues and organs and provide a special means of communications .
Blood is called – The river of life
BLOOD
Antoni van leeuwenhock- pioneer microscopy-blood
William Hewson – father of haematology Paul Ehrlich- poineer in use of dyes William Castle- extrinsic and intrinsic factors
Through the eyes of the past :
William Harvey 1628 background for blood transfusion
Richard Lower 1665 -1st blood transfusion - dog
1st human transfusion- 1667-sheep Jean Baptiste Denis - sheep to man
Lavoisier discovered- 18th century role of blood in transporting O2 from lungs to the tissues.
Karl landsteiner 1901 ->O-A-B blood groups 1940 -> Rh blood group (WIENER)
Respiration: transport of O2 and CO2. Transport: hormone, nutrients, metabolic
waste. Excretion of metabolic wastes to the kidney,
lungs and skin. Regulation of body temperature by
distribution of body heat. Defense against infections (WBCs,
antibodies). Maintenance of acid-base balance. Nutrition: transport of absorbed food
material.
FUNCTIONS OF BLOOD:
Specific gravity:-Whole blood:1.055 -1.065 kg/m³
Plasma: 1.024 -1.028 kg/m³ • Viscosity: 5-6 times that of water. Mass:6-8% of the body weight. Blood volume:~ 8% of body weight.~ 86%
(ml/kg body weight). 5-6 Liters in adults, [Infants have a larger blood volume in proportion to body weight than adults]. Osmotic pressure: 7-8 atmosphere at body
temperature
Physical properties of blood:
Generally , blood is red in color due to a pigment present in blood called haemoglobin.
Arterial blood is scarlet red while venous blood is purple red.
Ph of blood is 7.4.
Color of blood :
Composition of Blood:An adult human has about 4–6 liters of blood .Blood consists of several types of cells floating around in a fluid called plasma.
1. The red blood cells (RBCs) contain haemoglobin, a protein that binds oxygen. RBCs transport oxygen and remove carbon dioxide from the tissues.
2. The white blood cells fight infection.3. The platelets help the blood to clot.4. The plasma contains salts and various
kinds of proteins .
Plasma proteins – albumin , globulin and fibrinogen.
Carbohydrates – glucose Non protein substances – creatin ,
creatinine, xanthine , hypoxanthine , urea and uric acid.
Enzymes and antibodies . Inorganic substances - k , mg,cl, iodide ,
iron and phosphate. Gases – oxygen , carbondioxide.
Other constituents of blood :
CONSTITUENTS PLASMA RBC WATER 91-95% 65% SOLIDS 8-9 % 35% PROTEIN 6-8 gm % 31-
33% SPECIFIC GRAVITY 1.026
Gross composition of Plasma and Blood Cells
The hematocrit (haematocrit), also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF)- volume percentage (%) of red blood cells in blood.
Anticoagulant added to whole blood in presence of EDTA , Oxalate, Citrate and Heparin – no clotting of blood
blood centrifuged in a hematocrit tube for 30 minutes at speed of 300 rpm.
tube is taken out and reading is taken.
PCV decreases in Anemia and is increased in Polycythemia.NORMAL PCV :In males – 40 to 45 %In females – 38 to 42 %
The sequence of settlement of blood components: i. At bottom – Red blood cells (Erythocytes)- 45% of whole blood
ii. In the middle - White Buffy coat (Leucocytes Thrombocytes and platelets- >1% of the whole blood)
iii. On the Top – Plasma (55% of whole blood)
Rate of Sedimentation of Erythrocytes. ESR –Non specific indicator of infection. ESR - For monitoring status of chronic
inflammatory diseases . Normal Values: i. For males: 3 to 10 mm/hr ii. For females: 5 to 15 mm/hr.
ERYTHROCYTE SEDIMENTATION RATE (ESR)
Red blood cells settle upon one another at the Bottom of the Test tube.
This pattern of settlement of red blood cells upon one another is known as “ Rouleaux formation”.
The rate of settlement of red blood cells - erythrocyte sedimentation rate or ESR.
ESR is measured by :i. Wintrobe ‘s methodii. Westergren ‘s method
Normal Values:i. For males: 3 to 10 mm/hrii. For females: 5 to 15 mm/hr.
Chronic inflammatory disease (collagen and vascular diseases) increases ESR.Polycythemia decreases ESR.
Some interferences which increase ESR: increased level of fibrinogen, gamma
globulins. technical factors: tilted ESR tube, high room
temperature. Some interferences which decrease ESR: abnormally shaped RBC (sickle cells,
spherocytosis). technical factors: short ESR tubes, low room
temperature, delay in test performance (>2 hours), clotted blood sample, excess anticoagulant, bubbles in tube.
WHOLE BLOOD
NO ANTICOAGULANT
CLOT FORMATION
CENTIFRUDGE CLOT +CLEAR YELLOWISH FLUID (SERUM)
SERUM ( PLASMA – FIBRINOGEN ) C
ENTIFRUDGE
Blood Plasma - Composed of approximately 90% water Includes many dissolved substances Nutrients, Salts (electrolytes), Respiratory gases,
Hormones, Plasma proteins, Waste products.
PLASMA
Plasma proteins - Most abundant solutes in plasma
Most plasma proteins are made by liver
Various plasma proteins include Albumin—regulates osmotic
pressure Globulin – transports harmones Clotting proteins—help to stem
blood loss when a blood vessel is injured
Antibodies—help protect the body from pathogens .
Acidosis - Blood becomes too acidic Alkalosis - Blood becomes too basic
NORMAL VALUESTotal proteins - 7.3 gm% (6.4 to 8.3gm%)
Serum albumin - 4.7 gm %
Serum globulin - 2.3 gm%
Fibrinogen - 0.3 gm%
A-G Ratio: 1.7
1. Proteins 2. Carbohydrates 3. Fats 4. Amino acids 5. Non protein nitrogenous substances: 6. Internal secretions like hormones. 7. Enzymes -- amylase, carbonic anhydrase,
alkaline phosphatase, acid phosphatase, lipase, esterase, protease and transaminase.
8. Antibodies -- immunoglobulins.
Organic Substances of Plasma
Sodium Calcium Potassium Magnesium Chloride Iodide Iron Phosphates Copper
GASES PRESENT IN PLASMA: O2 & CO2
Inorganic Substances of Plasma
Help in coagulation of blood- fibrinogen Defense mechanism - gamma globulin Transport of harmones - albumin and
globulin Maintain acid base balance in blood Provide viscosity to blood Help in ESR regulation Help in maintaining suspension stability of
RBCS Produce trephone bodies in blood culture
along with WBCS
FUNCTIONS OF PLASMA PROTEINS
Blood levels of some important substances
Erythrocytes - Red blood cells (RBCs) Leukocytes - White blood cells (WBCs) blood Platelets
Formed Elements of blood
RED BLOOD CELLS Erythrocytes (red blood
cells or RBCs) - Main function is to carry oxygen .
Anatomy of circulating erythrocytes
Biconcave disks, essentially bags of hemoglobin, anucleate (no nucleus).
RBCS :Normal size : 7.5 microns in diameter and thickness 2.5 microns at periphery and 1 micron at the center.
Total Number Of RBCs:Average :
4-5 millions per mm³In males : 5 million per mm ³In females : 4.5 per mm ³
Homeostatic imbalance of RBCs : Anemia is a decrease in the oxygen-
carrying ability of the blood . Sickle cell anemia (SCA) results from
abnormally shaped hemoglobin . The red blood cells become sickle shaped. Polycythemia is an excessive or abnormal
increase in the number of erythrocytes .
RBCs are destroyed in spleen. Spleen is called - graveyard of RBCs.
Crucial in the body’s defense against diseases Originates from the same hemocytoblast stem cell as the red cells and platelets.
Produced normally in a proportion of about1/700 the number of red cells.
Colorless, have nuclei and granules which can be made visible by staining.
These are complete cells, with a nucleus and organelles.
Able to move into and out of blood vessels (diapedesis) .
4,000 to 11,000 WBC per cubic millimeter of blood .
Leukocytes (White Blood Cells)
: Leukocytosis / WBC count above 11,000
leukocytes/mm³ Generally indicates an infection
Leukopenia - Abnormally low leukocyte level Commonly caused by certain drugs such as
corticosteroids and anticancer agents Leukemia - Bone marrow becomes
cancerous, turns out excess WBCs.
Disorders of WBCs
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
List of the WBCs from most to least abundant :
Granulocytes - Granules in their cytoplasm can be stained, include basophils, eosinophils & neutrophils (BEN).
Have observable granules when stained. Neutrophils are 60-65% of leukocytes, the most common
wbc, they perform active and passive phagocytes. PMN leucocytes (Polymorphonuclear = many shaped
nucleus) Agranulocytes - Lack visible cytoplasmic granules, Include
lymphocytes and monocytes.
Types of leukocytes :
Lymphocytes - Play an important role in the immune response
Monocytes - Function as macrophages . Important in fighting chronic infection .
Types of Agranulocytes
Platelets - Needed for the clotting process
Normal platelet count = 250,000- 300,000/mm³.
platelet life: new platelets released from megakaryocytes remain functional till 7-11 days. old platelets are
decomposed in the liver and spleen.
BLOOD PLATELETS - THROMBOCYTESFunction of blood platelets:
1. platelets are responsible for wound healing .
2. platelets attach to the exposed vessel3. platelets change fibrinogen into fibrin this fibrin creates a mesh onto which red blood cellscollect and clot the clot stops more blood from leaving the body 4.prevents bacteria from entering the body.
RBC COUNT- Men : 4- 5 millions / mm³ Women : 4.5million / mm³ Total number of red cells = 4 – 5 millions / mm³ WBC COUNT - Men and women : 4000 – 11000/ mm³ PLATELETS : Men and women - 25 , 000/ mm³ Hb - Men14 –16 g/l Women - 12 –16 g / l PCV (Haematocrit): Men :0.42 –0.52 l/l Women :0.37 –0.47 l/l
Normal Values --
HAEMOGLOBINIron-containing protein that binds strongly, but reversibly to oxygen. Each hemoglobin molecule has four oxygen binding sites .Each erythrocyte has 250 million hemoglobin molecules .Normal blood contains 12–18 g of hemoglobin per 100 mL blood.
Structure : Globular and Conjugated protein, (Haem+
Globin). Made of 4 subunits (Quarternary structure) 4 globins + 4 haems → Haemoglobin. Binds O2 to Haemgroup to form
Oxyhaemoglobin. Hb+ 4O2→Hb(O2)4
General Description of Hb :Hemoglobin, a protein (a major solute) found in the red blood cells, contains Fe (iron) and serves as the principal transporter of molecular oxygen in the blood of humans as well as in many other animals. The hemoglobin picks up oxygen in the lungs and transfers it to the tissues where it is used by cells.
There are two major parts of hemoglobin: 1. Heme: A porphyrin with an Fe in the center. Porphyrin rings are found throughout biological
systems and serve many different roles including photosynthesis in green plants, delivering O2 in muscles (myoglobin) and transporting O2 in blood (hemoglobin).
2. Globin: Globin is the protein (polypeptide) surrounding the heme. Nomenclature:globin + heme (Fe2+) = hemoglobinglobin + heme (Fe3+) = methemoglobinThe overall structure of haemoglobin consists of four chains – two alfa and two beta chains
When hemoglobin is carrying O2 it is called oxyhemoglobin and when it is not carrying O2 it is known as deoxyhemoglobin.
Deoxy and oxyhemoglobin have different colors, thus explaining why blood in our arteries (oxyhemoglobin) is brighter red than the blood in our veins.
Oxygen binds to the Fe of the heme group because it has lone pairs which can coordinate to the Fe.
Features Of Haemoglobin
In Adults:Hb : ~ 97% α2β2HbF: <1% α2γ2HbA2: 2.5 – 3.5% α2 δ2 At Birth:HbF: β2 γ2HbA :α2 β2During Embryonic life:Hb Gower 1Hb Gower 2Hb Portland
Types Of Haemoglobins at various life stages
Hb + 0 2 - oxyhemoglobin Hb + C02 – carbhemoglobin Hb + CO – carboxyhemoglobin Hb + S - Sulfhemglobin Hb + potassium ferricyanide -
Methemoglobin
Derivatives of haemoglobin
In Lungs: High PO2, ↓H+,
↓CO2→high affinity of Hb for O2 (O2dissociation curve shifts to left).
In Tissues Low P O2, ↑H+,
↑CO2, ↑2,3 DPG →Low affinity of Hb for O2 (O2dissociation curve shifts to right )
THE BOHR EFFECT
Increase in the concentration of carbon dioxide will displace oxygen from hemoglobin and binding of Oxygen with Hemoglobin in turn will displace Carbon dioxide from blood. This phenomenon is referred to as the Haldane Effect.
HALDANE EFFECT
Coagulation is clotting of blood. Injured tissues release tissue factor (TF) . Prothrombin activator converts prothrombin
to thrombin (an enzyme) . Thrombin joins fibrinogen proteins into hair-
like molecules of insoluble fibrin Fibrin forms a meshwork (the basis for a
clot). Blood usually clots within 3 to 6 minutes .
Blood Coagulation and its Pathways:
BLOOD CLOTTING FACTORS
EXTRINSIC PATHWAYThe extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system. This pathway is quicker than the intrinsic pathway. ( Factors involved – III-VII-X-V .)
INTRINSIC PATHWAY :Begins to trauma to blood itself.( Factors involved -III, XII-XI-IX-VIII-X-V)
Interactions between the pathways:
Factor XIIa enhances Factor VII activity.
The VII-TF complexes that form during the extrinsic pathway can activate Factor IX of the intrinsic pathway, and this ability is augmented by the presence of Factor Xa.
Interaction between two pathways:
CLOT RETRACTION Serum = plasma - fibrinogen Role of calcium - in clot retraction Role of vitamin K- prothrombin and VII,IX and X Diff b/w extrinsic and intrinsic pathways extrinsic pathway- 15 sec – explosive intrinsic pathway – 1 to 6 min - slower
Endothelial surface factors - smoothness prevent contact activaton
glycocalyx repels clotting factors and platelets
protein Thrombomodulin + thrombin complex activates – protein C (inactivate V and VIII)
Antithrombin action of Fibrin and Antithrombin III prevents blood clotting inside the body.
HEPARIN inactivates – IX,X,XI,XII
Prevention of blood clotting in normal vascular system- intravascular anticoagulants
Lysis of blood clot inside the blood vessel – Fibrinolysis Plasma protein – euglobulin called plasminogen
(profibrinolysin) when activated become plasmin (fibrinolysin)
Plasmin digests fibrin fibres as well as coagulant factors I,II, V, VIII and XII
LYSIS OF BLOOD CLOT
HEPARIN- IV inj 0.5to 1 mg/kg body wt postpone clotting by 3 to 4 hr
Coumarin derivatives- Dicoumoral and Warfarin inhibit action of vit k
EDTA – removes calcium from blood . Oxalate compounds- calcium oxalate Citrates – Na, NH3,K citrate Citrate used in blood bank as acid citrate
dextrose (ACD) or citrate phosphate dextrose (CPD) to store blood.
Other- genetically engineered steptokinase for treating intravascular clots
Chemical agents to prevent clotting-ANTICOAGULANTS
Bleeding time is the interval between the moment when bleeding starts and the moment when bleeding stops. Normal bleeding time (Duke’s method) is to 4 minutes. Bleeding time is prolonged in purpuras, but normal in coagulation disorders like haemophilia.
Bleeding time is noted as in Duke’s method. Normal value is 2 to 7 minutes
Bleeding time :
Physical method to prevent blood clotting
Substance which accelerate the process of coagulation of blood are called hemostatic agent or procoagulants
THROMBIN SNAKE VENOM proteolytic enzymes enhance clotting by activating
clotting factors EXTRACTS OF LUNGS AND THYMUS thromboplastin -- rapid blood coagulation SODIUM OR CALCIUM ALGINATE activate Hageman factor OXIDIZED CELLULOSE activate Hageman factor
PROCOAGULANTS
BLEEDING TIME 2 Methods – DUKES method –> 2 – 6 min IVY’S method -> 3 – 6 min
Prolonged in purpura
CLOTTING TIME Capillary glass tube method -> 3 – 8 min at 370c LEE and WHITE method – glass tube 6-12 min - silicon tube 20-60 min Prolonged in hemophilia.
TESTS FOR CLOTTING
PROTHROMBIN TIME (PT) Time taken by blood to clot after adding
tissue thromboplastin is called prothrombin time.
PT indicates total quantity of prothrombin present in blood.
Normal PT –> 10 - 12 seconds. Prolonged in defeciency of prothrombin &
factors I, V, VII and X. Normal in hemophilia.
Clotting time is the interval between the moment when bleeding starts and the moment when the fibrin thread is first seen.
Normal value is 3 to 10 minutes. Vitamin K dependent factors are 2 , 7, 9 and
10, which help in coagulation of blood .
Clotting time :
Undesirable Clotting - : Thrombus - A clot in an unbroken blood
vessel Can be deadly in areas like the heart . Embolus - A thrombus that breaks away and
floats freely in the bloodstream Can later clog vessels in critical areas such
as the brain .
Coagulation of blood inside the blood vessel -thrombosis
Normally, blood does not clot in blood vessel because --
All clotting factors are in inactive form.
Smooth endothelial lining of blood vessels
Continuous movement of blood Natural anticoagulants like heparin
THROMBOSIS
Thrombocytopenia - Platelet deficiency Even normal movements can cause bleeding
from small vessels requiring platelets for clotting
Hemophilia - Hereditary bleeding disorder where normal clotting factors are missing.
Bleeding Disorders
HEMOPHILIA A – deficiency of factor VIII
HEMOPHILIA B ( CHRISTMAS DISEASE) – Deficiency of factor IX
HEMOPHILIA C- deficiency of factor XII WON WILIBRAND DISEASE – Bleeding
time is increased.
Types of Heamophilia :
Haemopoisis :The process of formation of blood. Erythropoisis : Formation of Erythrocytes. Leucopoisis : Formation of Leucocytes Thrombopoisis : Formation of Thrombocytes.
Haemopoisis
PROCESS PRODUCT Erythropoesis RBCS
Leucopoiesis WBCS
Granulopoiesis GRANULOCYTES
Lymphopoiesis LYMPHOCYTES
Megakaryocytes PLATELETS
Fetal Life 1-2 months - Yolk Sac 2-6 months - Spleen 1-9 months – Liver From 4 months –bone marrow At birth - bone marrow Adult life – bone marrow Red blood cells are destroyed in spleen. Spleen is called graveyard of RBCS.
Site of Haemopoisis
1. vitamin K 2. vitamin B 12 3. viamin C 4. iron 5. erythopoietin harmone – secreted by kidney 6. BPA – bursa promoting activity
FACTORS NECESSARY FOR FORMATION OF BLOOD:
Human Blood Groups: Blood contains genetically determined
proteins . Antigens (a substance the body recognizes as
foreign) may be attacked by the immune system .
Antibodies are the ―recognizers , are proteins produced in response to antigen
Blood is typed by using antibodies that will cause blood with certain proteins to clump (agglutination) .
The presence of both antigens A and B is called type AB .
The presence of antigen A is called type A . The presence of antigen B is called type B . The lack of both antigens A and B is called type
O . Blood type AB can receive A, B, AB, and O
blood (Universal recipient) . Blood type B can receive B and O blood Blood type A can receive A and O blood Blood type O can receive O blood (Universal
donor) .
Universal Acceptor and Universal Donor:
The AB0 and Rhesus (Rh) systems - used for blood transfusion.Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals.
Blood Transfusion People with blood group O are called "universal donors" and people with blood group AB are called "universal receivers."
Blood group A blood group A, has A antigens on the surface of RBCs and B antibodies in blood plasma.
Blood group Bblood group B, has B antigens on the surface of RBCs and A antibodies in blood plasma.
AB0 blood grouping system
Blood group AB blood group AB, has both A and B antigens on the surface of RBCs and no A or B antibodies at all in blood plasma.
Blood group Oblood group O (null), has neither A or B antigens on the surface RBCs but both A and B antibodies are present in blood plasma.
SEROLOGYSerology: This is a direct detection of the ABO antigens.
This form of testing involves two components:
a) Antibodies that are specific at detecting a particular ABO antigen on RBCs. b) Cells that are of a known ABO group
Blood Group
Antigens Antibodies Can give blood to
Can receive blood from
AB A and B None AB AB, A, B, O
A A B A and AB A and O
B B A B and AB B and O
O None A and B AB, A, B, O O
Rh Blood Groups : Named a/ c presence or
absence of one of eight Rh antigens (agglutinogen D).
Most Americans and Asians are Rh+ (Rh positive) .
Problems can occur in mixing Rh+ blood into a body with Rh– (Rh negative) blood .
First discovered in Rhesus monkeys in 1939, by Philip Levine and Rufus Stetson .
Hemolytic Disease of new born : Danger occurs only when the
mom is Rh– and the dad is Rh+, and the child inherits the Rh+ factor.
Rho GAM shot can prevent buildup of anti-Rh+ antibodies in mother.
The mismatch of an Rh– mother carrying an Rh+ baby can cause problems for the unborn child .
The first pregnancy usually proceeds without problems .
The immune system is sensitized after the first pregnancy .
In a second pregnancy, the mother’s immune system produces antibodies to attack the Rh+ blood (hemolytic disease of the newborn) .
HARRISON – TEXTBOOK OF GENERAL MEDICINE 21TH EDITION
GYTON – TEXTBOOK OF PHYSIOLOGY 12 TH EDITION
DAVIDSON TEXTBOOK OF MEDICINE – 20 TH EDITION
www.redcross.org/blood www.americasblood.org/ www.bloodjournal.org/
BIBILOGRAPHY
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