BLOOD

COMPOSITION AND FUNCTIONS

Blood
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 Blood
Formed Elements : Erythrocytes, Leukocytes , Platelets & Plasma.

Blood composition
55% 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 SMEAR

Physical Characteristics and Volume

Sticky and metallic tasting Color: Scarlet = O2 rich; Dull red = O2 poor Heavier than H2O; 5X thicker

pH = 7.35 - 7.45
Temp = 38C or 100.4F (higher than normal) 8% body weight; 5 - 6 liters

COMPONENTS OF BLOOD

Centrifuged blood

55% Plasma: Serum and fibrinogen <1% Buffy Coat: White blood cells (leukocytes) 45% Red blood cells (erythrocytes) Hematocrit: RBC volume = ~45%

plasma (55%) red blood cells (5-6-million /ml) white blood cells (5000/ml) platelets

Plasma

Straw-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 transports soluble food molecules waste products hormones antibodies

COMPONENTS OF BLOOD: PLASMA

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

PLASMA PROTEINS
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 a globulin: Transport lipids and fat soluble vitamins. b globulin: Transport lipids and fat soluble vitamins. g 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

COMPONENTS OF BLOOD: PLASMA

Composition of plasma is kept relatively constant:

replenishes blood proteins Respiratory system and kidneys maintain pH (acidosis = too acid; alkalosis = too basic)
Liver

Plasma helps maintain body heat.

COMPONENTS OF BLOOD: FORMED ELEMENTS

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 Half-life ~ 120 days. Contain 280 million hemoglobin with 4 heme chains (contain iron).

RED BLOOD CELLS SPECIALISATIONS

1) biconcave shape 2) no nucleus extra space inside 3) contain haemoglobin the oxygen carrying molecule 250million molecules / cell

increases the surface area so more oxygen can be carried

FORMED ELEMENTS
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

HAEMOGLOBIN

gives red blood cells their colour can carry up to 4 molecules of O2 associates and dissociates with O2 contains iron

Red blood cells (RBCs)

transport oxygen specialised to do this Also carry some CO2

COMPONENTS OF BLOOD: FORMED ELEMENTS

Erythrocytes or RBCs While 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.

FUNCTION OF HAEMOGLOBIN

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

ANEMIA: A DECREASE IN THE OXYGENCARRYING CAPACITY OF THE BLOOD

Anemia results from: Lower # RBCs Deficient hemoglobin

ANEMIAS FROM LOWER RBCS:

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.

ANEMIA: ABNORMAL HEMOGLOBIN

Sickle Cell Anemia: Deficient hemoglobin - a point mutation changes a single amino acid.

EXCESSIVE RBCS (ERYTHROCYTES)

Polycythemia - abnormal increase in erythrocytes,

caused by: Bone marrow cancer High altitudes

Thickens and circulation

slows

blood,

impairs

LEUKOCYTES OR WHITE BLOOD CELLS (WBCS)

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

LEUKOCYTES
Have nucleus, mitochondria, & amoeboid ability Can squeeze through capillary walls (diapedesis)

Granular
Include

leukocytes help detoxify foreign substances & release heparin

eosinophils, basophils, & neutrophils

LEUKOCYTES

Agranular leukocytes are phagocytic & produce antibodies

Include

lymphocytes & monocytes

TYPES OF LEUKOCYTES

TYPES OF LEUKOCYTES
Granulocytes

Granules in their cytoplasm can be stained Include neutrophils, eosinophils, and basophils Lack visible cytoplasmic granules Include lymphocytes and monocytes

Agranulocytes

GRANULOCYTES

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

AGRANULOCYTES

Lymphocytes

Nucleus fills most of the cell Play an important role in the immune response Largest of the white blood cells Function as macrophages Important in fighting chronic infection

Monocytes

LYMPHOCYTE

LYMPHOCYTES
Provide a specific immune response to infectious diseases. There are 2 types: - T-cells & B-cells They produce antibodies.

MONOCYTES

PLATELETS

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.

PHAGOCYTES

Monocytes and macrophages Provide a non-specific response to infection

HEMATOPOIESIS
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 by variety of cytokines

Leukopoiesis is formation of WBCs

Stimulated
=

autocrine regulators secreted by immune system

HEMATOPOIESIS
Formation of blood cells 2 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.

ERYTHROPOIESIS

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.

LEUKOPOIESIS
Cytokines stimulate different types and stages of WBCs production

Multi potent growth factor-1 , interleukin-1 , and interleukin3:

Stimulate development of different types of WBC cells. Stimulates development of neutrophils. Simulates development of monocytes and eosinophil's.

Granulocyte-colony stimulating factor:

Granulocyte-monocyte colony stimulating factor:

ERYTHROPOIESIS
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 Vessels

Arteries 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. Increasing blood flow into capillaries. Decreasing blood pressure.

Vasodilation: Arteries relax:

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 System

Components: 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.

ABO Blood Type

Antigen A

Antigen B

Antibody anti-A

Antibody Anti-B

yes

no

no

yes

no

yes

yes

no

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.

RED BLOOD CELL ANTIGENS

ABO system: Major group of antigens of RBCs. Type A:

Only A antigens present. Only B antigens present. Both A and B antigens present.

Type B:

Type AB:

Type O:

Neither A or B antigens present.

RBC ANTIGENS
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.

RBC ANTIGENS

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 -.

TRANSFUSION REACTIONS

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 doesnt 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

TRANSFUSION REACTIONS

If blood types do not match, the recipients antibodies attach to donors RBCs and agglutinate. Type O Universal donor. Recipients antibodies cannot agglutinate the donors RBCs. Type AB Universal recipient Lack the anti-A and anti-B antibodies. Cannot agglutinate donors RBCs.

RH FACTOR

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.

TRANSFUSION REACTIONS
If blood types don't match, recipients antibodies agglutinate donors RBCs Type O is universal donor because lacks A & B antigens

Insert fig. 13.6

Recipients antibodies wont agglutinate donors Type O RBCs

Type AB is universal recipient because doesnt make anti-A or anti-B antibodies

Wont RBCs

agglutinate

donors

BLOOD CLOTTING ( Hemostatic mechanisms)

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.

ROLE OF PLATELETS
Platelets don't stick to intact endothelium because of presence of prostacyclin (PGI2--a prostaglandin) & NO

Keep clots from forming & are vasodilators

ROLE OF PLATELETS
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

ROLE OF PLATELETS
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

ROLE OF FIBRIN

Platelet plug becomes infiltrated by meshwork of fibrin Clot now contains platelets, fibrin & trapped RBCs

Platelet plug undergoes plug contraction to form more compact plug CONVERSION OF FIBRINOGEN TO FIBRIN

Can occur via 2 pathways:

Intrinsic pathway clots damaged vessels & blood left in test tube

Initiated by exposure of blood to negatively charged surface of glass or blood vessel collagen

This activates factor XII (a protease) which initiates a series of clotting factors Ca2+ & phospholipids convert prothrombin to thrombin Thrombin converts fibrinogen to fibrin which polymerizes to form a mesh

Damage outside blood vessels releases tissue thromboplastin that triggers a clotting shortcut (= extrinsic pathway)

FUNCTION OF PLATELETS
Platelets normally repelled away from endothelial lining by prostacyclin (prostaglandin). Do not want to clot normal vessels.

DAMAGE TO ENDOTHELIAL WALL

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.

PLATELET RELEASE REACTION

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.

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).

CONVERSION OF FIBRINOGEN TO 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.

EXTRINSIC PATHWAY
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.

DISSOLUTION OF CLOTS
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.

DISSOLUTION OF CLOTS

When damage is repaired, activated factor XII causes activation of kallikrein

Kallikrein
Plasmin

converts plasminogen to plasmin

digests fibrin, dissolving clot

ANTICOAGULANTS

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