Dr. Moattar Raza Rizvi NRS237, Physiology

Distributes•Oxygen and nutrients (removes waste products)•Hormones delivered to target organsRegulates•Body temperature, pHProtects•Against blood/fluid loss via hemostasis (coagulation)•Against infection via contribution to inflammatory and immune responses.

• Sticky• Opaque• Salty-metallic taste• Color varies according to oxygen content• More dense than water and 5x more

viscous • pH: 7.35-7.45 (reservoir for bicarbonate

ions)• Temperature: 38°C• Volume (4-6 litres; adult).

• Blood is the body’s only fluid tissue (a connective tissue)

• 2 major components– Liquid = plasma (55%)– Formed elements (45%)

• Erythrocytes, or red blood cells (RBCs)• Leukocytes, or white blood cells (WBCs)• Platelets or Thrombocytes

Withdraw blood and place in tube

1 2 Centrifuge

Plasma(55% of whole blood)

Formed elements

Buffy coat:leukocyctes and platelets(<1% of whole blood)

Erythrocytes(45% of whole blood)

• Hematocrit • Males: 47% ± 5%• Females: 42% ± 5%

• Hematocrit • Males: 47% ± 5%• Females: 42% ± 5%

• Blood plasma components:– Water = 90-92%– Proteins = 6-8%

• Albumins; maintain osmotic pressure and viscosity of the blood

• Globulins– Alpha and beta globulins are used for transport purposes– Gamma globulins are the immunoglobulins (IgG, IgA, etc)

• Fibrinogen; a clotting protein– Organic nutrients – glucose, carbohydrates, amino acids– Electrolytes – sodium, potassium, calcium, chloride, bicarbonate – Nonprotein nitrogenous substances – lactic acid, urea,

creatinine– Respiratory gases – oxygen and carbon dioxide

• Formed elements comprise 45% of blood• Erythrocytes, leukocytes, and platelets make up the

formed elements– Only WBCs are complete cells– RBCs have no nuclei or organelles, and platelets are just

cell fragments• Most formed elements survive in the bloodstream for

only a few days• Most blood cells do not divide but are renewed by

cells in bone marrow

• Biconcave disc– Folding increases surface area (30% more surface area)– Plasma membrane contains spectrin

• Give erythrocytes their flexibility• Anucleate, no centrioles, no organelles

– End result - no cell division– No mitochondria means they generate ATP anaerobically

• Filled with hemoglobin (Hb) - 97% of cell contents– Hb functions in gas transport

• Hb + O2 HbO2 (oxyhemoglobin)• Most numerous of the formed elements

– Females: 4.3–5.2 million cells/cubic millimeter– Males: 5.2–5.8 million cells/cubic millimeter

• Erythrocytes are dedicated to respiratory gas transport• Hemoglobin reversibly binds with oxygen and most

oxygen in the blood is bound to hemoglobin– Hb functions in gas transport

• Hb + O2 HbO2 (oxyhemoglobin)

• Composition of hemoglobin– A protein called globin

• made up of two alpha and two beta chains– A heme molecule

• Each heme group bears an atom of iron, which can bind to one oxygen molecule

• Each hemoglobin molecule thus can transport four molecules of oxygen

• Oxyhemoglobin – hemoglobin bound to oxygen– Oxygen loading takes place in the lungs

• Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues (reduced Hb)

• Carbaminohemoglobin – hemoglobin bound to carbon dioxide

– Carbon dioxide loading takes place in the tissues

The life span of an erythrocyte is 100–120 daysTravels about 750 miles in that time

Iron is transported from liver in blood plasma by beta-globulins as transferrin

RBC Destruction1.RBC damaged by squeezing through capillaries2.Macrophages phagocytize damaged RBC in spleen/liver3.Hemoglobin decomposes – heme & globin4.Heme decomposes – iron & biliverdin5.Iron is stored to be used later6.Some biliverdin converted to bilirubin7.Biliverdin/bilirubin excreted in bile as pigments8.Globin broken down into amino acids

Imbalance

Reduces O2 levels in blood

Erythropoietin stimulates red bone marrow

Enhanced erythropoiesis increases RBC count

Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Imbalance

Start

Kidney (and liver to a smaller extent) releases erythropoietin

Increases O2-carrying ability of blood

• Hematopoiesis – blood cell formation• Production of Erythrocytes: Erythropoiesis

– Occurs in the red bone marrow (myeloid tissue) • Axial skeleton and girdles• Epiphyses of the humerus and femur• Marrow contains immature erythrocytes

• The % volume occupied by red blood cells is known as the hematocrit.

• Volume occupied by white blood cells is relatively small.

• Leukocytes, the only blood components that are complete cells:– Larger than RBC – Up to 3 times larger

• Two major types of leukocytes– Granulocytes: Neutrophils, Eosinophils, Basophils– Agranulocytes: Monocytes, Lymphyocytes

• Normal WBC Count 4,800 - 10,000/cubic millimeter• Number and percentage of each WBC helps diagnose certain

diseases– Leukocytosis – WBC count over 11,000/mm3

• Normal response to bacterial or viral invasion– Leukopenia - a decrease in WBC count below 4,800/mm3 – Leukemia - a cancer of WBC

• Diapedesis: Can squeeze through small spaces and leave blood circulation

• Functions of WBC – Fighting Foreign Microorganisms

• Functions of WBC – Fighting Foreign Microorganisms• WBC release chemicals that dilate blood vessels

• Inflammatory response• More blood to area – redness, swelling

• Damaged cells release chemicals that attract other WBCs• Positive chemotaxis

• Pus forms from bacteria, WBCs, and damaged cells• Until all foreign microorganisms are “dead”

Are all phagocytic cellsCell Type Characteristic features Major Functions

Neutrophils Account for 65-75% of total WBC’sMultilobed nucleusAKA “polys” or PMN’s (polymorphonuclear)

Ingest and destroy invading microorganismsParticipate in acute inflammation

Eosinophils Eosinophils account for 1–4% of WBCs Bilobed nucleus

Phagocytic especially against parasitic infection

large multicellular parasites such as tapeworms and hookworms

Basophils Account for 0.5-1% of all WBCsHave U- or S-shaped nuclei

Migrate to tissues to become mast cells; release of histamine contributes to inflammation

Helps in allergic reactions

Cell Type Characteristic features Major Functions

Monocyte Monocytes account for 3–7% of leukocytes They are the largest leukocytesThey have purple-staining, U- or kidney-shaped nuclei

They leave the circulation, enter tissue, and differentiate into macrophages which protect against viruses, certain intracellular bacterial parasites, and chronic infections.

Lymphocyte Account for 20-25% or more of WBCs and:Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm

Most important cells of the immune systemThere are two types of lymphocytes: T cells and B cellsT cells - attack foreign cells directlyB cells give rise to plasma cells, which produce antibodies

• Not complete cells, fragments• No nucleus• Less than half the size of RBC• Lives for about 10 days• Platelet Counts: 150,000‐450,000 per μL blood• Their granules contain serotonin, Ca2+, enzymes, ADP,

and platelet-derived growth factor (PDGF)• Platelets function in the clotting mechanism by forming

a temporary plug that helps seal breaks in blood vessels• Platelets not involved in clotting are kept inactive by

Nitric Oxide (NO) and prostaglandins

• RBC membranes have glycoprotein antigens on their external surfaces

• These antigens are:– Unique to the individual – Recognized as foreign if transfused into another individual– Promoters of agglutination and are referred to as

agglutinogens

• Presence or absence of these antigens is used to classify blood groups

• The ABO blood groups consists of:– Two antigens (A and B) on the surface of the RBCs – Two antibodies in the plasma (anti-A and anti-B)

• An individual with ABO blood may have various types of antigens and spontaneously preformed antibodies

• Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

Blood Group AB is Universal Recipient Blood Group O is Universal Donor

• There are 4 blood types– A, B, AB, O– Type A has “A” antigen, and B antibodies– Type B has “B” antigen, and A antibodies– Type AB has “A” and “B” antigen, and NO antibodies– Type O has NO antigen and “A” and “B” antibodies

Named after the rhesus monkeys in which itwas first studied• Many Rh factors, mostly antigen

• Presence of the Rh agglutinogens on RBCs is indicated as Rh+; 85% of population is +

• Lack of antigen indicated as Rh -; 15% of popn.• Anti-Rh antibodies are not spontaneously formed only in Rh–

individuals

• Rh antibodies created in Rh individuals in response ‐to Rh antigens on Rh+ RBC

• If an Rh individual receives Rh+ blood‐• First time : usually ok

• Second time : RBC have become sensitized to Rh+ blood; Rh antibodies will attack and agglutinate the Rh+ RBC

When a blood vessel ruptures, local vasoconstriction (decrease in the caliber of blood vessels) occurs to decrease blood flow to the area.

Platelets and clotting factors become activated when exposed to the collagen layer of the damaged blood vessel.

Platelets clump together (aggregate) by binding to the collagen, forming a loose platelet plug.

• Three Coagulation Pathways– Extrinsic pathway: release of chemicals from broken blood vessel or

damaged tissue• Begins in the vessel wall

• Outside bloodstream

– Intrinsic pathway: blood contact with foreign surfaces in absence of

tissue• Begins with circulating proenzymes

• Within bloodstream

– Common pathway• Where intrinsic and extrinsic pathways converge

Hemostasis

• The Extrinsic Pathway

– Damaged cells release tissue factor (TF)

– TF + other compounds = enzyme complex

– Activates Factor X

• The Intrinsic Pathway

– Activation of enzymes by collagen

– Platelets release factors (e.g., PF–3)

– Series of reactions activates Factor X

Hemostasis

• The Common Pathway

– Forms enzyme prothrombinase

– Converts prothrombin to thrombin

– Thrombin converts fibrinogen to fibrin

Hemostasis

• Stimulates formation of tissue factor

– Stimulates release of PF-3

– Forms positive feedback loop (intrinsic and

extrinsic)

• Accelerates clotting

Hemostasis

The Coagulation Phase of Hemostasis

Hemostasis

The Coagulation Phase of Hemostasis

Hemostasis

• Calcium Ions, Vitamin K, and Blood Clotting

– Calcium ions (Ca2+) and vitamin K are both

essential to the clotting process

Hemostasis

• Clotting: Area Restriction

– Anticoagulants (plasma proteins)

• Antithrombin-III

• Alpha-2-macroglobulin

– Heparin

– Protein C (activated by thrombomodulin)

– Prostacyclin

Hemostasis

• Clotting تخثر 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

Complete the following questions: 1.Diapedesis is the process by which the WBC’s comes out of blood capillaries. 2.Erythropoiesis is the formation of red blood cells. 3.Erythrocytopenia is the decrease in the number of RBC.4.Hematocrit is the percentage of blood cells in the blood. 5.Instrument used to determine RBC count Hematocytometer6.Hemolysis is breaking of RBC.7.Hemometer instrument used to know percentage of hemoglobin in blood. 8.Leukocytosis is increase in number of WBC’s9.Erythrocytosis is increase in number of RBC’s.10.Leukopenia is decrease in number of WBC’s. 11.Red blood cells in human does not contain nucleus and mitochondria 12.Give the terms used for decrease in RBC and WBC count.13.Blood is fluid connective tissue

1. Write the functions of blood?2. Write the composition of blood?3. Write the different types of White blood cells?4. What is hemoglobin and its function?5. What is the life span of RBC?6. Write the functions of platelets?7. Name the different types of blood groups in our body. 8. Name the antigens and antibodies present in blood group A, B,

AB and O?9. Name any 3 blood anticoagulants? 10. Name the plasma proteins found in blood with function? 11. Define blood coagulation? The property of blood to change

from fluid to get state within a few minutes after it comes in contact with air is blood coagulation.

12. What is the role of vitamin K? Vitamin K is essential for the formation of blood clot.