Blood - Lecture notes 1 PDF

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Blood...

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BLOOD Blood is viscous. Viscous is the thickness or stickiness of the fluid. Higher viscosity thicker consistency. 5 times thicker than water. Higher viscosity  harder possibility to flow through a vasculature. High viscosity  high blood pressure. Blood have higher temperature because as the blood flow through the vasculature, it creates some level of friction and resistance with the vessels and arteries. Blood is slightly basic in nature. We carry about 4-6 L of blood and makes up 8% of the body mass. The most common type of cell in the body is the erythrocytes (RBC). Composition of Whole Blood Composition of blood  

Plasma (55%) Formed elements (45%)

Function

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Complex transport medium that performs vital pickup and delivery services for the body Key component of the body’s heat-regulating mechanism

Composition of Blood Plasma Overview   

Liquid part of the blood; clear, straw-colored fluid 90% water and 10%solutes Tend to be lighter in nature

Proteins (6-8% of plasma)     

Synthesized in the liver Important in maintaining normal blood circulation Albumins: help maintain osmotic balance of blood Globulins: essential part of immunity mechanism. One type are antibodies. Fibrinogen: key role in blood clotting

Red blood cells & Hematocrit levels Hematocrit – volume percent of RBCs in whole blood  

Normal whole blood is about 55% plasma and 45% RBCs (hematocrit 45%) Average o Men 45%: 5,500, 00/mm 3 o Women 42%: 4,800,00/mm3

Erythrocytes (Red blood cells or RBCs) Structure of RBCs   

Contain no nucleus, ribosomes, mitochondria, or other organelles Primary component: hemoglobin (Hb) Shape: biconcave disks – large surface area (SA) relative to its volume, compared to sphere to provide enormous potential for gas exchange

Function of RBCs   

Critical role in transport of O2 and CO2; depends on hemoglobin Contains enzyme carbonic anhydrase. Anhydrase – dissociates the H2CO3 to bicarbonate The reaction occurs in the RBC, but can result on plasma (reacts slower and not more favourable)

Hemoglobin (Hb) Overview  

Each RBC contain 200-300 million molecules of hemoglobin Each Hb can bind to 4 O2 molecules: each RBC can transport 1 billion O2 molecules

Structure 

Hemoglobin is made up of 4 globin (protein) chains, each attached to a heme group with 1 Fe(iron) atom

Gas transport  

1 O2 may bind to each heme group: each Hb can bind and transport up to 4 O2 molecules CO2 is also transported by Hb, small portion is bound to amino acids in the globin part, but most is transported as HCO3- ions

Erythropoiesis (RBC Formation) Rate of RBC formation  

200 billion per day in an adult Equivalent to the rate of destruction: Homeostatic mechanism

General process   

RBC formation begins in the red bone marrow with hematopoietic stem cells which go through several stages of development to become erythrocytes Regulated by hormone Erythropoietin (EPO) which is synthesized by kidney The entire maturation process requires approximately 4 days

Life Cycle of RBCs Life spans of a circulating RBC averages 105-120 days Macrophages phagocytose aged, abnormal, or fragmented RBCs

Hemoglobin is broken down, and amino acids, iron, and bilirubin are released

Having a hypoxic state can cause the chain reaction in the erythropoietin Pulmonary disease and anemia can be associated with hypoxia Blood types (ABO system) Overview    

Blood type: depends on the type of cell markers or antigens present on RBC membranes Presence/absence of blood antigens A and B determines a person’s blood type Additional antigens exist that are not as important clinically but still may cause occasional problems During a blood transfusion, care must be taken to prevent a transfusion reaction

ABO system 

Every person’s blood belongs to one of four ABO blood groups, according to antigens present on RBC membranes

ABO blood types    

Type A: Antigen A is present on RBC’s Type B: Antigen B is present on RBC’s Type AB: Both antigen A and antigen B are present on RBCs (universal recipients) Type O: Neither antigen A nor antigen B is present on RBCs (universal donors)

Antigens characteristics of each blood type are bound to the surface of RBCs. The antibodies of each blood type are found in the plasma and exhibit unique structural features that permit agglutination to occur upon exposure to the appropriate antigen. Rh System What is RH? 

Another antigen present on the RBC cell membrane

Rh-positive blood  

Rh antigen is present on the RBCs A+, B+, O+, AB+

Rh-negative blood

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RBCs have no Rh antigen A-, B-, O-, AB-

Anti-Rh antibodies

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Not normally present in blood; anti-Rh antibodies can appear in Rh-negative blood if it has come in contact with Rh-positive RBCs. Normally during pregnancy blood does not mix. During labour and delivery, blood between mother and fetus can mix. Having Rh+ and Rh- can create a complication.

Erythroblastosis Fetalis   

Rh-positive blood cells enter mother’s bloodstream during delivery on a Rh-positive baby. If not treated, mother’s body produces anti-Rh antibodies. A later pregnancy with a Rh-negative baby proceeds normally because baby’s blood has no Rh antigens. A later pregnancy with a Rh-positive baby may result in erythroblastosis fetalis. Anti-Rh antibodies enter the baby’s blood supply and cause agglutination of RBCs with the Rh antigen.

Leukocytes or White Blood Cells (WBCs) Overview  

White blood cells (WBCs), or leukocytes, do not contain pigments but appear white when collected together (like snowflakes) Five different types have been classified according to their staining characteristics

Function 

WBC numbers are clinically significant because they change with certain abnormal conditions

Formation of WBC (leukopoiesis)   

Leukocytes and platelets, like erythrocytes, mature from undifferentiated hematopoietic stem cell Myeloid “marrow” line produces granular leukocytes and monocytes Lymphoid stem cell line produces only lymphocytes

Types of Leukocytes 

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Granulocytes – WBC that contain large granules in the cytoplasm o Neutrophils (65% of the total WBC count)  Highly mobile and very active phagocytic cells: capable of diapedesis  Cytoplasmic granules contain lysosomes o Eosinophils (2-5% of circulating WBCs)  Numerous in mucous lining of respiratory and digestive tracts  Weak phagocytes; release chemicals of immunity; provide protection against infections caused by parasitic worms and help regulate allergic reactions o Basophils (0.5-1% of circulating WBCs)  Motile and capable of diapedesis  Cytoplasmic granules contain histamine and heparin (plays role in allergic reactions) Agranulocytes – WBCs that have no cytoplasmic granules o Lymphocytes (25% of circulating WBCs)

o

 Smallest WBCs: play important roles in immunity  T lymphocytes directly attack an infected or a cancerous cell  B lymphocytes produce antibodies against specific antigens Monocytes  Largest leukocytes; mobile and highly phagocytic cells

Moving to the Site of Injury 1. Damaged or injured tissue cause mast cells to release chemotactic factors 2. These chemotactic agents attract neutrophils in the blood vessels 3. Neutrophils first adhere to the inside of the blood capillary in a process called pavementing or margination 4. Neutrophils then squeeze through the wall of a blood vessel to get to the site of injury or infection a process called diapedesis 5. Chemotaxis (movement directly by chemical attraction) makes neutrophils migrate toward the highest concentration of chemotactic factor near injury site 6. Once it gets to the injury site, it can then begin its immune functions Thrombocytes or Platelets Structure 

In circulating blood, platelets are small, pale bodies that appear as irregular spindles or oval disks

Function (properties)    

Play an important role in hemostasis (blood clotting) Agglutination: clumping together of RBCs Adhesiveness: becomes sticky when in contact with damaged capillary wall. Sticks to each other and to tissues Aggregation: clumping together

Formation (thrombopoiesis) and life span of platelets   

Begins with the stimulation of precursor cells called megakaryoblasts Mature megakaryocytes are large in size and multinucleated and can rupture into 2000-3000 platelets Platelets have an average life span of about 7 days

Steps in Hemostasis Hemostasis: stoppage of blood flow out of blood vessels 1. Vasoconstriction causes temporary closure of a damaged vessel and lessens blood loss 2. Platelet plug formation a. Injury to vessel wall b. Platelets become “sticky”, adhering to damaged endothelial lining and each other (aggregation) 1-5 seconds after c. Physical platelet plug is formed: it secretes several chemicals involved in the coagulation process (agglutination)

d. Secondary role in bacterial defense 3. Clot formation (coagulation): formation of net of fibrin fibers that traps RBCs a. Activation of either intrinsic or extrinsic pathway of coagulation b. Release of clotting factors from both injured tissue cells and sticky platelets at the injury site (which form temporary platelet plug) to start a series of chemical reactions that eventually result in the formation of thrombin c. Formation of fibrin and trapping of blood cells to form a clot Blood Clotting (Coagulation) Overview 

Series of chemical reactions that take place quickly in a certain sequence to result in a net of fibers that traps RBCs

Stage of coagulation   

Stage 1: Activation pathways – intrinsic or extrinsic Stage 2 (start of common pathway): thrombin formation Stage 3: Fibrin clot formation

Pathways  

Extrinsic clotting pathways: activated by damaged tissues Intrinsic clotting pathways: activated by factors normally present, or intrinsic to, the blood

Common steps in both pathways  

Both pathways result in synthesis of prothrombinase Both pathways require platelets, Ca2+, prothrombin, Factor XIII, fibrinogen

Clot Dissolution (Fibrinolysis) Overview

 

Physiological mechanism that dissolves clots Two opposing processes of clot formation and fibrinolysis go on continuously

Plasminogen 

Inactive plasma protein that can be activated by several substance released form damaged cells

Plasmin  

Enzyme that catalyzes that hydrolysis of fibrin strands, dissolving the clot slowly Activated by chemicals released from damaged cells (thrombin, factor XII, tissue plasminogen activator, and lysosomal enzymes)...