The average human has 5 litres of blood(Average Blood Volume is 4 to 6 liters).

It is a transporting fluid It carries vital substances to all parts of the

body Blood is the only fluid tissue. Blood is a complex connective tissue in which

living cells, the formed elements, are suspended in the nonliving fluid called plasma.

Composition of BloodFormed Elements : Erythrocytes, Leukocytes , Platelets &

Plasma.

BloodBlood

Blood composition55% Plasma (fluid matrix of water, salts, proteins, etc.)45% Cellular elements: Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood.

Contain hemoglobin which transport oxygen and CO2. White Blood Cells (WBCs): 5,000-10,000 WBCs/ml of

blood. Play an essential role in immunity and defense. Include:

Lymphocytes: T cells and B cells Macrophages: (phagocytes) Granulocytes: Neutrophils, basophils, and eosinophils.

Platelets: Cellular fragments, 250,000- 400,000/ml of blood. Important in blood clotting.

HUMAN BLOOD SMEARHUMAN BLOOD SMEAR

Physical Characteristics and Volume

Sticky and metallic tasting…Color: Scarlet = O2 rich; Dull red = O2 poorHeavier than H2O; 5X thickerpH = 7.35 - 7.45Temp = 38ºC or 100.4ºF (higher than normal)8% body weight; 5 - 6 liters

Centrifuged blood

45% Red blood cells (erythrocytes)Hematocrit: RBC volume = ~45%

(leukocytes)<1% Buffy Coat: White blood cells

55% Plasma: Serum and fibrinogen

plasma (55%)

red blood cells(5-6-million /ml)

white blood cells(5000/ml)

platelets

PlasmaStraw-colored liquid.Consists of H20 and dissolved solutes.Ions, metabolites, hormones, antibodies.Na+ is the major solute of the plasma.liquid part of blood

Plasma transportssoluble food moleculeswaste productshormones antibodies

90% of plasma is water: >100 other substances in plasma: salts

(electrolytes), nutrients, gases, hormones, plasma proteins, various wastes and products of cell metabolism.

Plasma proteins: Constitute 7-9% of plasma. Provide the colloid osmotic pressure needed to draw H20 from

interstitial fluid to capillaries. Maintain blood pressure.

Albumin:. Maintains osmotic pressure of blood. Clotting proteins Antibodies

Constitute 7-9% of plasma Three types of plasma proteins: albumins, globulins, &

fibrinogen Albumin accounts for 60-80, plasma protein made by the

liver, Creates colloid osmotic pressure that draws H20 from interstitial fluid into capillaries to maintain blood volume & pressure

Globulins carry lipids globulin: Transport lipids and fat soluble vitamins. globulin: Transport lipids and fat soluble vitamins. globulin: Antibodies that function in immunity. Gamma globulins are antibodies

Fibrinogen Constitutes 4% of plasma proteins. Important clotting factor. Converted into fibrin during the clotting process. Serum is fluid left when blood clots

Composition of plasma is kept relatively constant: Liver replenishes blood proteins… Respiratory system and kidneys maintain pH

(acidosis = too acid; alkalosis = too basic)

Plasma helps maintain body heat.

Erythrocytes or RBCs Anucleate - they lack a nucleus Filled with hemoglobin which carries oxygen Biconcave discs = greater surface area for

gas exchange. 5X106 cells/mm3 of Half-life ~ 120 days. Contain 280 million hemoglobin with 4 heme chains

(contain iron).

RED BLOOD CELLS SPECIALISATIONSRED BLOOD CELLS SPECIALISATIONS

2) no nucleus extra space inside

3) contain haemoglobin

the oxygen carrying molecule

250million molecules / cell

1) biconcave shape

increases the surface area so more oxygen can be carried

Are erythrocytes (RBCs) & leukocytes (WBCs)

RBCs are flattened biconcave discs Shape provides increased

surface area for diffusion Lack nuclei & mitochondria Each RBC contains 280

million hemoglobins

HAEMOGLOBINHAEMOGLOBIN

gives red blood cells gives red blood cells their colour their colour

can carry up to 4 can carry up to 4 molecules of Omolecules of O22

associates and associates and dissociates with Odissociates with O22

contains ironcontains iron

Red blood cells (RBCs)

transport oxygen specialised to do this Also carry some CO2

Erythrocytes or RBCsWhile number of RBCs in the blood is

important….hemoglobin is the key.The more hemoglobin molecules the

RBCs contain, the more oxygen they can carry.

1RBC - 250 million molecules of hemoglobin, each binding 4 molecules of oxygen.

When there is a high concentration of oxygen e.g in the alveoli haemoglobin combines with oxygen to form oxyhaemoglobin. When the blood reaches the tissue which have a low concentration of oxygen the haemoglobin dissociates with the oxygen and the oxygen is released into body tissues

FUNCTION OF HAEMOGLOBINFUNCTION OF HAEMOGLOBIN

Anemia results from: Lower # RBCs Deficient hemoglobin

Hemorrhagic anemia: sudden hemorrhage Hemolytic anemia: lysis of RBCs from bact.

infection Pernicious anemia: lack of B12 Aplastic anemia: depression/destruction of

bone marrow by cancer, radiation, meds.

Sickle Cell Anemia: Deficient hemoglobin - a point mutation

changes a single amino acid.

Polycythemia - abnormal increase in erythrocytes, caused by: Bone marrow cancer High altitudes

Thickens and slows blood, impairs circulation

Complete cells (nuclei, mitochondria and organelles) Move in amoeboid fashion. Can squeeze (leave the blood vessels through)

capillary walls (diapedesis), respond to chemicals Almost invisible, so named after stains. Neutrophils are the most abundant WBC, accounts for 50 – 70% of

WBCs. Involved in immune function. Crucial for defense. Positive chemotaxis: they respond to chemical signals and move toward

damage or threats. Body increases amount in response to infection Leukocytosis: more than 11,000 cells/mm3 indicates

infection Leukopenia: abnormally low, usually due to corticosteroids

and chemotherapy.

White blood cells

the bodies “defence” part of the immune system much larger than RBCs far fewer have a nucleus 4000-13000 per mm3

2 types: phagocytes and lymphocytes

Have nucleus, mitochondria, & amoeboid ability Can squeeze through capillary walls

(diapedesis) Granular leukocytes help detoxify foreign

substances & release heparin Include eosinophils, basophils, & neutrophils

Agranular leukocytes are phagocytic & produce antibodies

Include lymphocytes & monocytes

Granulocytes Granules in their cytoplasm can be stained Include neutrophils, eosinophils, and basophils

Agranulocytes Lack visible cytoplasmic granules Include lymphocytes and monocytes

Neutrophils Multi-lobed nucleus with fine granules Act as phagocytes at active sites of infection

Eosinophils Large brick-red cytoplasmic granules Found in response to allergies and parasitic worms

Basophils Have histamine-containing granules Initiate inflammation

Lymphocytes Nucleus fills most of the cell Play an important role in the immune

response Monocytes

Largest of the white blood cells Function as macrophages Important in fighting chronic infection

Provide a specific immune response toinfectious diseases.There are 2 types: -

- T-cells & B-cellsThey produce antibodies.

MONOCYTESMONOCYTES

Also called thrombocytes. Derived from ruptured multinucleate cells

(megakaryocytes) Smallest of formed elements.

Are fragments of megakaryocytes. Lack nuclei.

Normal platelet count = 300,000/mm3

Survive 5-9 days Have amoeboid movement. Important in blood clotting: Constitute most of the mass of the clot.

Release serotonin to reduce blood flow to area. Secrete growth factors

Maintain the integrity of blood vessel wall.

PHAGOCYTESPHAGOCYTES Monocytes and macrophages

Provide a non-specific response to infection

HEMATOPOIESISHEMATOPOIESIS

Is formation of blood cells from stem cells in marrow (myeloid tissue) & lymphoid tissue

Erythropoiesis is formation of RBCs Stimulated by erythropoietin (EPO) from

kidney Leukopoiesis is formation of WBCs

Stimulated by variety of cytokines= autocrine regulators secreted by immune

system

Formation of blood cells2 types of hematopoiesis:Erythropoiesis:

Formation of RBCs.Leukopoiesis:

Formation of WBCs.Occurs in myeloid tissue (bone marrow of long bones) and lymphoid tissue.Stem cells differentiate into blood cells.

Active process. 2.5 million RBCs are produced every second. Regulated by erythropoietin.

Erythropoietin binds to membrane receptors, stimulating cell division.

Old cells are destroyed in spleen and liver. Iron recycled back to myeloid tissue to be

reused in RBC synthesis. Need iron, vitamin B12 and folic acid for

synthesis.

Cytokines stimulate different types and stages of WBCs production

Multi potent growth factor-1 , interleukin-1 , and interleukin-3:

Stimulate development of different types of WBC cells.

Granulocyte-colony stimulating factor: Stimulates development of neutrophils.

Granulocyte-monocyte colony stimulating factor: Simulates development of monocytes and

eosinophil's.

2.5 million RBCs are produced/sec

Lifespan of 120 days

Old RBCs removed from blood by phagocytic cells in liver, spleen, & bone marrow Iron recycled back

into hemoglobin production

Types of Blood VesselsArteries and Arterioles

Carry blood away from heart to body. Have high pressure.Have thick muscular walls, which make them elastic and contractile.

Vasoconstriction: Arteries contract: Reducing flow of blood into capillaries. Increasing blood pressure.

Vasodilation: Arteries relax: Increasing blood flow into capillaries. Decreasing blood pressure.

Capillaries Only blood vessels whose walls are thin enough to

permit gas exchange. Blood flows through capillaries relatively slowly,

allowing sufficient time for diffusion or active transport of substances across walls.

Only about 5 to 10% of capillaries have blood flowing through them. Only a few organs (brain and heart) always carry full load of blood.

Blood flow to different organs is controlled by pre capillary sphincters of smooth muscle.

Veins and Venules

Collect blood from all tissues and organs and carry it back towards heart.Have low pressure and thin walls.Veins have small valves that prevent backflow of blood towards capillaries, especially when standing. If the valves cease to work properly, may result in:

Varicose veins: Distended veins in thighs and legs. Hemorrhoids: Distended veins and inflammation of

the rectal and anal areas.

Lymphatic and Immune SystemComponents: Lymph, lymphatic vessels, bone marrow, thymus, spleen, and lymph nodes.Functions:

Defends against infection: bacteria, fungi, viruses, etc.

Destruction of cancer and foreign cells. Synthesis of antibodies and other immune

molecules. Synthesis of white blood cells.

Homeostatic Role: Returns fluid and proteins that have leaked from

blood capillaries into tissues. Up to 4 liters of fluid every day. Fluid returned near heart/venae cavae.

RBC Antigens & Blood Typing

The most well known and medically important blood types are in the ABO group. They were discovered in 1900 and 1901 at the University of Vienna by Karl Landsteiner in the process of trying to learn why blood transfusions sometimes cause death and at other times save a patient. In 1930, he belatedly received the Nobel Prize for this discovery.

All humans and many other primates can be typed for the ABO blood group. There are four principal types: A, B, AB, and O. There are two antigens and two antibodies that are mostly responsible for the ABO types. The specific combination of these four components determines an individual's type in most cases.

ABOBlood Type   Antigen

AAntigen

B  Antibody

anti-AAntibody

Anti-B

A   yes no no yes

B   no yes yes no

O   no no yes yes

AB   yes yes no no

 

People with type A blood will have the A antigen on the surface of their red cells . As a result, anti-A antibodies will not be produced by them because they would cause the destruction of their own blood. However, if B type blood is injected into their systems, anti-B antibodies in their plasma will recognize it as alien and burst or agglutinate the introduced red cells in order to cleanse the blood of alien protein.

Individuals with type O blood do not produce ABO antigens. Therefore, their blood normally will not be rejected when it is given to others with different ABO types. As a result, type O people are universal donors for transfusions, but they can receive only type O blood themselves. Those who have type AB blood do not make any ABO antibodies. Their blood does not discriminate against any other ABO type. Consequently, they are universal receivers for transfusions, but their blood will be agglutinated when given to people with every other type because they produce both kinds of antigens.

It is easy and inexpensive to determine an individual's ABO type from a few drops of blood. A serum containing anti-A antibodies is mixed with some of the blood. Another serum with anti-B antibodies is mixed with the remaining sample. Whether or not agglutination occurs in either sample indicates the ABO type. It is a simple process of elimination of the possibilities. For instance, if an individual's blood sample is agglutinated by the anti-A antibody, but not the anti-B antibody, it means that the A antigen is present but not the B antigen. Therefore, the blood type is A.

ABO system: Major group of antigens of RBCs.

Type A: Only A antigens present.

Type B: Only B antigens present.

Type AB: Both A and B antigens present.

Type O: Neither A or B antigens

present.

Each person inherits 2 genes that control the production of ABO groups.

Type A: May have inherited A gene from each

parent. May have inherited A gene from 1 parent

and O gene from the other.

Type B: May have inherited B gene from each

parent. May have inherited B gene from 1 parent

and O gene from the other parent. Type AB:

Inherited the A gene from one parent and the B gene from the other parent.

Type O: Inherited O gene from each parent.

People with blood group 0 Rh - are called "universal donors" and people with blood group AB Rh+ are called "universal receivers."

Rh+ blood can never be given to someone with Rh - blood, but the other way around works. For example, 0 Rh+ blood can not be given to someone with the blood type AB Rh -.

People with Type A blood make antibodies to Type B RBCs, but not to Type A

Type B blood has antibodies to Type A RBCs but not to Type B

Type AB blood doesn’t have antibodies to A or B

Type O has antibodies to both Type A & B

If different blood types are mixed, antibodies will cause mixture to agglutinate

If blood types do not match, the recipient’s antibodies attach to donor’s RBCs and agglutinate.

Type O Universal donor. Recipient’s antibodies cannot agglutinate

the donor’s RBCs. Type AB Universal recipient

Lack the anti-A and anti-B antibodies. Cannot agglutinate donor’s RBCs.

Another group of antigens found on RBCs. Rh positive:

Have these antigens. Rh negative:

Do not have these antigens. Significant when Rh negative mother give

birth to Rh positive baby. At birth, mother may become exposed to Rh

positive blood of fetus. Mother at subsequent pregnancies may

produce antibodies against the Rh factor.

If blood types don't match, recipient’s antibodies agglutinate donor’s RBCs

Type O is “universal donor” because lacks A & B antigens Recipient’s antibodies

won’t agglutinate donor’s Type O RBCs

Type AB is “universal recipient” because doesn’t make anti-A or anti-B antibodies Won’t agglutinate donor’s

RBCs

Insert fig. 13.6

Is cessation of bleeding Promoted by reactions initiated by vessel

injury Breakage of endothelial lining exposes collagen

proteins causing: Vasoconstriction. Platelet plug. Web of fibrin.

Platelets don't stick to intact endothelium because of presence of prostacyclin (PGI2--a prostaglandin) & NO Keep clots from forming & are vasodilators

Damage to endothelium allows platelets to bind to exposed collagen von Willebrand factor increases bond by binding to

both collagen & platelets Platelets stick to collagen & release ADP,

serotonin, & thromboxane A2 = platelet release reaction

Serotonin & thromboxane A2 stimulate vasoconstriction, reducing blood flow to wound

ADP & thromboxane A2 cause other platelets to become sticky & attach & undergo platelet release reaction This continues until platelet plug is formed

Platelets normally repelled away from endothelial lining by prostacyclin (prostaglandin).

Do not want to clot normal vessels.

Exposes sub endothelial tissue to blood. Platelet release reaction:

Endothelial cells secrete von Willebrand factor to cause platelets to adhere to collagen.

Platelet secretory granules release ADP, serotonin and thromboxane A2.

Serotonin and thromboxane A2 stimulate vasoconstriction.

ADP and thromboxane A2 make other platelets “sticky”.

Platelets adhere to collagen. Produce platelet plug. Strengthened by activation of plasma

clotting factors.

Platelet plug strengthened by fibrin. Clot reaction:

Contraction of the platelet mass forms a more compact plug.

Conversion of fibrinogen to fibrin occurs. Fluid squeezed from the clot is called

serum (plasma without fibrin).

Intrinsic Pathway Initiated by exposure of blood to a

negatively charged surface (collagen). This activates Factor XII (protease), which

activates other clotting factors. Ca++ and phospholipids convert prothrombin

to thrombin. Thrombin converts fibrinogen to fibrin. Produces meshwork of insoluble fibrin

polymers.

Thromboplastin is not a part of the blood, so called extrinsic pathway.

Damaged tissue release a thromboplastin.

Thromboplastin initiates a short cut to formation of fibrin.

Activated factor XII converts an inactive molecule into the active form (kallikrein).

Kallikrein converts plasminogen to plasmin.

Plasmin is an enzyme that digests the fibrin.

Clot dissolution occurs.

When damage is repaired, activated factor XII causes activation of kallikrein Kallikrein converts plasminogen to plasmin

Plasmin digests fibrin, dissolving clot

Clotting can be prevented by Ca+2 chelators (e.g. sodium citrate or EDTA) or heparin which activates antithrombin

III (blocks thrombin) Coumarin blocks clotting by

inhibiting activation of Vit K Vit K works indirectly by reducing Ca+2

availability