Anatomy

Blood is a liquid connective tissue costing of cells surrounded by a liquid matrix( plasma)

Cellular components are red blood cells, white blood cells, platelets, and plasma.

Plasma consist of water, proteins, and other solutes

Blood is transported by

Formed elements and dissolved molecules and ions Arrives oxygen from and carbon dioxide to lungs Transports nutrients, hormones, and heat and waste products Is known as delivery system for the body

Blood is regulated by

Body temp. Absorbs heat from the body cells Released from blood at body’s surface As blood is transported through the vessels of the skin It regulate body pH Absorbs acids and base from cell bodies Contains chemicals buffer that binds and release hydrogen ions As blood regulates fluid balance It contains leukocytes, plasma proteins, other modules Helps protect the body from harmful substances Platelets and plasma proteins help protect the body against blood los Plasma is composed of 92% of water,7% of plasma proteins, and dissolved molecules and ions that make up 1% Also contains extracellular fluid Similar composition to interstitial fluid The protein concentration in plasma than interstitial fluid The plasma proteins in blood consider a colloid The proteins in the plasma consist of albumin, globulins, fibrinogen, and other clotting proteins, enzymes, and some hormones Most are produced in the liver and other are produced by leukocytes and other organs

Colloid osmotic pressure exerted by plasma proteins To prevent loss of fluid from the blood as it moves through the capillaries It helps maintain blood volume and blood pressure and can decreased with disease Like liver disease results from the decreased production of plasma Kidney damage is increased by elimination of plasma proteins which result in fluid loss from blood and results in fluid retention in internal space

Albumins The smallest and most abundant plasma proteins They make up 58% of total proteins and exerts the greatest colloid osmotic pressure Also maintains blood volume and pressure and acts as transport proteins, carry ions, hormones, and some lipids Globulins Are the 2nd largest group of plasma proteins and make up 47% of the total proteins It transports some water insoluble molecules, hormones, metals, and ions It’s also referred to as immunoglobulin or antibodies and plays a part in body’s defense

Fibrinogen

Make up 4% of total proteins and contributes to blood clot formation Also following trauma it is converted to insoluble fibrin strands and plasma with clotting proteins removed referred to as serum

Regulatory proteins make up less than 1% of total proteins This include enzymes to accelerate chemical reactions and some hormones like insulin

Blood is consider a solution It contains dissolved organic and inorganic molecules and ions includes electrolyte, nutrients, gases, and waste products and has a polar or charged substance dissolving easily It also as non polar molecules requiring transporter proteins Nitrogenous by products of metabolism- lactic acid, urea, creatinine Nutrients- glucose, carbohydrates, and amino acids Electrolyte- Na+ (sodium), k+ (potassium), ca2+ (calcium), Cl- (Chlorine), HCO3- (bicarbonate)

Respiratory gasses- O2(oxygen), CO2 ( carbon dioxide) Hormones

Lymphocytes are able to live for years while most other blood cells live for hours, days, or weeks

The number of red blood cels and platelets remains rather steady while that of white blood cells varies depending on invading pathogens and other foreign antigens

The process of producing blood cells is hemopoiesis or (hematopoieis)

Pluripotent stem cells differentiate into each of the different types of blood cells

Hematopoiesis occurs in red bone marrow of axial skeleton, girdles and proximal epiphyses of humerus and femur

Hemocytoblast or hematopoietic stem cells gives rise to all formed elements The hormones and growth factor push the cell toward specific pathways of blood cell development Also new blood cells enter blood sinusoids

Erythrocytes or red blood cells are Biconcave discs, anucleate essentially no organelles Is filled with hemoglobin (Hb) for gas transport and contains the plasma protein membrane protein spectrin and other proteins

Provides flexibility to change shape as necessary and are the major factor contributing to blood viscosity Structural characteristics contribute to gas transport Biconcave shape- hugs the surface area relative to volume 97% hemoglobin not counting water

\ Red blood cells contain the protein hemoglobin that is used to carry oxygen to all cells and to carry some carbon dioxide to the lungsEach hemoglobin molecule contains and iron ion which allows each molecule to bind to four oxygen molecules

Red blood cells have no nucleus or other organelles and are Biconcave discs that allow then to carry oxygen more efficiently

Red blood cells also contain carbonic anhydrase which catalyze the conversion of carbon dioxide and water to carbonic acid

Carbonic acid transport about 70% of carbon dioxide in the plasma Red blood cells live for only about 120 days Dead cells are removed from the circulation by the spleen and liver Breakdown products from the red blood cells are recycled and reused Hemoglobin (Hb) structure have protein globin of 2 alpha and 2 beta chains Heme pigment bonded to each globin chain Iron atom in each heme can bind to one oxygen molecule Each hemoglobin molecule can transport 4 oxygen molecules

The oxygen loading in the lungs produce oxyhemoglobin that are ruby red

Oxygen unloading in the tissues produce deoxyhemeoglobin that are dark red

Carbon dioxide loading in tissues produce carbaminohemeglobin that carries 20% of carbon dioxide in the blood

Erythropoietin is a hormone released by the kidneys in response to hypoxia or a lowered oxygen concentration stimulates differentiation of hematopoietic stem cells into erythrocytes

Reticulocytes are immature red blood cells that enter the the blood circulation and mature in 1 to 2 days

A Hemocytoblast is transferred into a proerythroblasts Proerythroblasts develops into early erythroblasts

Ribosomes synthesis
Hemoglobin accumulation
Ejection of the nucleus and formation of Reticulocytes Reticulocytes then become mature erythrocytes

Erythropoietin (EPO) is a direct stimulus for erythropoiesis and released by kidneys in response to hypoxia

It causes hypoxia to hemorrhage or increase red blood cells destruction reduces red blood count numbers Insufficient hemoglobin like iron deficiency or reduced availability of oxygen at high altitudes The effects of EPO or erythropoietin is more rapid maturation of committed bone marrow cells It also increases circulation Reticulocytes count in 1-2 days Testosterone also enhanced EPO production resulting in higher red blood cells counts in males

Homeostatic imbalance like sickle cell disease is a genetic anemia where oxygen carrying capacity of the blood is reduced

The red blood cells of individuals with this disease contain hemoglobin-s (Hb-S) which causes red blood cells bend into the sickle shape when it gives up oxygen to the interstitial fluid

Sickle cell anemia is defective gene codes for abnormal hemoglobin (HbS) which causes red blood cells to become sickle shaped Normal sickle erythrocytes has normal hemoglobin amino acid sequence in the beta chain

White blood cells or leukocytes contain a nucleus and organelles but no hemoglobin

Leukocytes are classified as: Granular containing vesicles that appear when the cells are stained The granular leukocytes are neutrophils, eosinophils, and basophils A granular contains no granules and are leukocyte, lymphocytes, and monocytes

White blood cells may live for serval months or years, their main function is to combat invading microbes

During an invasion many white blood cells are able to leave the bloodstream and collect at sites of invasion This process is known as emigration (diapedesis)

In general, an elevation in the white blood count usually indicates an infection or inflammation

A low blood white blood count many develop due to several causes A differential white blood cell count will help to determine if a problem exits

Leukocyte disorders Leukopenia are abnormally low white blood count which are drug induced Leukemias Is a cancerous condition involving white blood cells and is named according to the abnormal white blood cells clone involved Myelocytic leukemia involves myeloblasts Lymphocytic leukemia involves lymphocytes Acute leukemia involves blast-type cells and primarily affects children Chronic leukemia is more prevalent in older people Bone marrow totally occupied with cancerous leukocytes Immature nonfunctional white blood cells in the blood stream Death caused by inertial hemorrhage and overwhelming infections Treatments include irradiation antileukemic drugs and stem cells transplants

Platelets are small fragments of megakaryocytic and the formation is regulated by thrombopoietin Platelets are a blue staining outer region with purple granules Granules contains serotonin, Ca2+ (calcium), enzymes, ADP, and platelet derived growth factor (PDGF) Form a temporary platelet plug that helps eat breaks in blood vessels Circulating platelets are kept inactive and mobile by NO and prostacyclin from endothelial cells of blood vessels

Hemostasis is a sequence of responses that stop bleeding

Vascular spasm are blood vessels constricts to limit blood escape. Smooth muscle contracts causing vasoconstriction of damaged blood vessels It triggers o the direct injury, chemicals released by endothelial cells and platelets and is pain reflexes
Platelets plug formation Platelets arrive at site of injury and stick to expose collagen fibers Injury to lining of the vessel exposes fibers, platelets adhere Platelets release chemicals that make nearby platelets sticky platelet plug forms Positive feedback cycle at the site of blood vessel injury, platelets stick to exposed collagen fibers with the help of Von Willebrand factor, a plasma protein They swell and become spiked and sticky to release chemicals messengers ADP causes more platelets to stick and release their contents Serotonin and thromboxane A2 enhance vascular spam and more platelets aggregation
Coagulation phase Cascade converts indicate proteins to active forms and from a blood clot Fibrin forms a mesh that traps red blood cells and platelets from clotting

Blood clotting involves several clotting (coagulation) factors •Blood clotting can be activated in one of 2 ways: ●Extrinsic pathway ●Intrinsic pathway •Both of these pathways lead to the formation of prothrombinase and, from there, the common pathway continues Blood clot formation

A set of reactions in which blood is transformed from a liquid to a gel •Reinforces the platelet plug with fibrin threads •Three phases of coagulation 1.Prothrombin activator is formed (intrinsic and extrinsic pathways) 2.Prothrombin is converted into thrombin (common pathway) 3.Thrombin catalyzes the joining of fibrinogen to form a fibrin mesh (common pathway)

2 pathways to prothrombin •Initiated by either the intrinsic or extrinsic pathway (usually both) •Triggered by tissue-damaging events •Involves a series of procoagulants •Each pathway cascades toward factor X •Factor X complexes with Ca2+ and factor V to form prothrombin activator (i.e. prothrombinase) •Intrinsic pathway • Is triggered by negatively charged surfaces (activated platelets, collagen, glass) •Uses factors present within the blood (intrinsic) •Extrinsic pathway •Is triggered by exposure to tissue factor (TF) or factor III (an extrinsic factor) •Bypasses several steps of the intrinsic pathway, so is faster The blood clot formation of common pathway Prothrombin coverts soluble fibrinogen into fibrin •Fibrin strands form the structural basis of a clot •Fibrin causes plasma to become a gel-like trap for formed elements •Thrombin (with Ca2+) activates factor XIII which: cross-links fibrin and strengthens and stabilizes the clot •Once the clot forms, it retracts (tightens) to pull the edges of the damaged vessel together •Vitamin K is needed for normal clot formation because it is used in the synthesis of 4 clotting factors •Small, unwanted clots are usually dissolved by plasmin, an enzyme that is part of the fibrinolytic system

Blood is characterized into different blood groups based on the presence or absence of glycoprotein and glycolipid antigens (agglutinogens) on the surface of red blood cells ●There are 24 blood groups and more than 100 antigens ●Because these antigens are genetically controlled, blood types vary among different populations ●Classification is based on antigens labeled A, B, or AB, with O being the absence of the antigens ●An additional antigen, Rh, is present in 85% of humans •Blood plasma usually contains antibodies (agglutinins) that react with A or B antigens •An individual will not have agglutinins against his or her own blood type

Typing and cross-matching are performed in order to determine a person’s blood type •A drop of blood is mixed with an antiserum that will agglutinate blood cells that possess agglutinogens that react with it At birth, small amounts of fetal blood leak into the maternal circulation •If the baby is Rh+ and the mother is Rh−, she will develop antibodies to the Rh factor •During her next pregnancy with an Rh+ baby, when she transfers antibodies to the fetus (a normal occurrence), transferred anti Rh antibodies will attack some of the fetus’ red blood cells causing agglutination and hemolysis

Chapter 20 The pericardium consists of an outer fibrous pericardium and an inner serous pericardium •The serous pericardium has 2 layers: 1.Visceral 2.Parietal Layers of the heart wall Epicardium-visceral layer of the serous pericardium 2.Myocardium •Spiral bundles of cardiac muscle cells •Fibrous skeleton of the heart: crisscrossing, interlacing layer of connective tissue •Anchors cardiac muscle fibers •Supports great vessels and valves •Limits spread of action potentials to specific paths 3.Endocardium-is continuous with endothelial lining of blood vessels The chambers of the heart include two upper atria and two lower ventricles Atria the receiving chamber Walls are ridged by pectinate muscles •Vessels entering right atrium •Superior vena cava •Inferior vena cava •Coronary sinus •Vessels entering left atrium •Right and left pulmonary veins Ventricles the discharging chamber Walls are ridged by trabeculae carneae •Papillary muscles project into the ventricular cavities •Vessel leaving the right ventricle •Pulmonary trunk •Vessel leaving the left ventricle •Aorta The right atrium receives blood from the superior and inferior vena cava and the coronary sinus The right ventricle receives blood from the right atrium and sends blood to the lungs The left atrium receives blood from the pulmonary veins

The left ventricles receives blood from the left atrium and sends blood all over the body

The fibrous skeleton of the heart: ●Forms the foundation for which the heart valves attach ●Serves as a point of insertion for cardiac muscle bundles ●Prevents overstretching of the heart valves ●Acts as an electrical insulator The valves of the heart open and close in response to pressure changes as the heart contracts and relaxes •When one set of valves is open, the other set is closed •Atrioventricular (AV) valves •Prevent back flow into the atria when ventricles contract •Tricuspid valve (right) •Bicuspid valve (left) •Semilunar (SL) valves •Prevent back flow into the ventricles when ventricles relax •Aortic semilunar valve •Pulmonary semilunar valve Blood returning to the heart fills atria, putting pressure against atrioventricular valves; atrioventricular valves are forced open. 1 Ventricles contract, forcing blood against atrioventricular valve cusps. 2 As ventricles fill, atrioventricular valve flaps hang limply into ventricles. 2 Atrioventricular valves close. 3 Atria contract, forcing additional blood into ventricles. 3 Papillary muscles contract and chordae tendineae tighten, preventing valve flaps from everting into atria. As ventricles contract and intraventricular pressure rises, blood is pushed up against semilunar valves, forcing them open. As ventricles relax and intraventricular pressure falls, blood flows back from arteries, filling the cusps of semilunar valves and forcing them to close. Equal volumes of blood are pumped to the pulmonary and systemic circuits •Pulmonary circuit is a short, low-pressure circulation •Systemic circuit blood encounters much resistance in the long pathways •Anatomy of the ventricles reflects these differences Coronary circulation The functional blood supply to the heart muscle itself •Blood flow through coronary arteries delivers oxygenated blood and nutrients to the myocardium •Branches arise from the ascending aorta •Right and left coronary (in atrioventricular groove), marginal, circumflex, and anterior interventricular arteries •Coronary veins remove carbon dioxide and wastes from the myocardium •Branches converge at the coronary sinus •Small cardiac, anterior cardiac, and great cardiac veins Cardiac muscle contraction Depolarization of the heart is rhythmic and spontaneous •About 1% of cardiac cells have automaticity— (are self-excitable; these are the pacemaker cells-autorhythmic fibers) It’s the APS from these cells that excite the contrctile fibers. •Gap junctions ensure the heart contracts as a unit •Long absolute refractory period (250 ms) •Depolarization opens voltage-gated fast Na+ channels in the sarcolemma •Reversal of membrane potential from –90 mV to +30 mV •Depolarization wave in T tubules causes the SR to release Ca2+ •Depolarization wave also opens slow Ca2+ channels in the sarcolemma •Ca2+ surge prolongs the depolarization phase (plateau) •Ca2+ influx triggers opening of Ca2+-sensitive channels in the SR, which liberates bursts of Ca2+ •E-C coupling occurs as Ca2+ binds to troponin and sliding of the filaments begins •Duration of the AP and the contractile phase is much greater in cardiac muscle than in skeletal muscle •Repolarization results from inactivation of Ca2+ channels and opening of voltage-gated K+ channels Cardiac muscle tissue Cardiac muscle cells are striated, short, fat, branched, and interconnected •Connective tissue matrix (endomysium) connects to the fibrous skeleton •T tubules are wide but less numerous; SR is simpler than in skeletal muscle •Numerous large mitochondria (25–35% of cell volume) •Intercalated discs: junctions between cells anchor cardiac cells •Gap junctions allow ions to pass; electrically couple adjacent cells •Desmosomes prevent cells from separating during contraction •Heart muscle behaves as a functional syncytium The conduction system Some cardiac muscle cells are self-excitable, and therefore, autorhythmic. These are the pacemaker cells or autorhythmicfibers ●These cells repeatedly generate spontaneous action potentials that then trigger heart contractions •These cells form the conduction system, which is the route for propagating action potentials through the heart muscle The conduction system Sinoatrial (SA) node (pacemaker) •Generates impulses about 75 times/minute (sinus rhythm) •Depolarizes faster than any other part of the myocardium 2.Atrioventricular (AV) node •Smaller diameter fibers; fewer gap junctions •Delays impulses approximately 0.1 second •Depolarizes 50 times per minute in absence of SA node input 3.Atrioventricular (AV) bundle (bundle of His) •Only electrical connection between the atria and ventricles 4.Right and left bundle branches •Two pathways in the interventricularseptum that carry the impulses toward the apex of the heart 5.Purkinje fibers •Complete the pathway into the apex and ventricular walls •AV bundle and Purkinje fibers depolarize only 30 times per minute in absence of AV node input Influence of conduction system The autorhythmic fibers in the SA node are the natural pacemaker of the heart because they initiate action potentials most frequently •Signals from the nervous system and hormones (like epinephrine) can modify the heart rate and force of contraction but they do not set the fundamental rhythm Extrinsic Innervation of the heart

Heartbeat is modified by the ANS •Cardiac centers are located in the medulla oblongata •Cardioacceleratory center innervates SA and AV nodes, heart muscle, and coronary arteries through sympathetic neurons •Cardioinhibitory center inhibits SA and AV nodes through parasympathetic fibers in the vagus nerves Sympathetic nervous system is activated by emotional or physical stressors •Norepinephrine causes the pacemaker to fire more rapidly (and at the same time increases contractility) •Parasympathetic nervous system opposes sympathetic effects •Acetylcholine hyperpolarizes pacemaker cells by opening K+channels •The heart at rest exhibits vagal tone (parasympathetic) •Atrial (Bainbridge) reflex: a sympathetic reflex initiated by increased venous return •Stretch of the atrial walls stimulates the SA node •Also stimulates atrial stretch receptors activating sympathetic reflexes Electrical events Depolarization is due to Na+ influx through fast voltage-gated Na+ channels. A positive feedback cycle rapidly opens many Na+ channels, reversing the membrane potential. Channel inactivation ends this phase. Plateau phase is due to Ca2+ influx through slow Ca2+ channels. This keeps the cell depolarized because few K+ channels are open. Repolarization is due to Ca2+ channels inactivating and K+ channels opening. This allows K+ efflux, which brings the membrane potential back to its resting voltage. Electrocardiogram (ECG or EKG): a composite of all the action potentials generated by nodal and contractile cells at a given time •Three waves 1.P wave: depolarization of SA node 2.QRS complex: ventricular depolarization 3.T wave: ventricular repolarization An EKG is a recording of the electrical changes that accompany each heart beat Heart sounds Two sounds (lub-dup) associated with closing of heart valves •First sound occurs as AV valves close and signifies beginning of systole •Second sound occurs when SL valves close at the beginning of ventricular diastole •Cardiac cycle: all events associated with blood flow through the heart during one complete heartbeat •Systole—contraction •Diastole—relaxation •Heart murmurs: abnormal heart sounds most often indicative of valve problems Phases of cardiac cycle One cardiac cycle consists of the contraction (systole) and relaxation (diastole) of both atria, rapidly followed by the systole and diastole of both ventricles Atrial systole -Ventricular filling AV valves are open 80% of blood passively flows into ventricles Atrial systole occurs, delivering the remaining 20% End diastolic volume (EDV): volume of blood in each ventricle at the end of ventricular diastole Ventricular systole Atria relax and ventricles begin to contract Rising ventricular pressure results in closing of AV valves Isovolumetric contraction phase (all valves are closed) In ejection phase, ventricular pressure exceeds pressure in the large arteries, forcing the SL valves open End systolic volume (ESV): volume of blood remaining in each ventricle Isovolumetric relaxation occurs in early diastole Ventricles relax Back flow of blood in aorta and pulmonary trunk closes SL valves and causes dicrotic notch (brief rise in aortic pressure) Cardiac output or C O Volume of blood pumped by each ventricle in one minute •CO = heart rate (HR) x stroke volume (SV) •HR = number of beats per minute •SV = volume of blood pumped out by a ventricle with each beat •At rest •CO (ml/min) = HR (75 beats/min)  SV (70 ml/beat) = 5.25 L/min •Maximal CO is 4–5 times resting CO in nonathletic people •Maximal CO may reach 35 L/min in trained athletes •Cardiac reserve: difference between resting and maximal CO

Regulation of a stroke SV = EDV – ESV •EDV stands for end diastolic volume in the ventricles, the amount of blood collecting in the ventricle during diastole •ESV stands for end systolic volume, blood remaining in ventricle after contraction •Three main factors affect SV •Preload •Contractility •Afterload Preload: degree of stretch of cardiac muscle cells before they contract (Frank-Starling law of the heart) •Cardiac muscle exhibits a length-tension relationship •At rest, cardiac muscle cells are shorter than optimal length •Slow heartbeat increases venous return •Increased venous return distends (stretches) the ventricles and increases contraction force

•Contractility: contractile strength at a given muscle length, independent of muscle stretch and EDV •Positive inotropic agents increase contractility •Increased Ca2+ influx due to sympathetic stimulation •Hormones (thyroxine, glucagon, and epinephrine) •Negative inotropic agents decrease contractility •Acidosis •Increased extracellular K+ •Calcium channel blockers Afterload: pressure that must be overcome for ventricles to eject blood •Hypertension (high BP) increases afterload, resulting in increased ESV and reduced SV Factors of increased cardiac output Regular aerobic exercise can: •Increase cardiac output •Increase HDL •Decrease triglycerides •Improve lung function •Decrease blood pressure •Assist in weight control Hemostasis imbalance Defects in the intrinsic conduction system may result in 1.Arrhythmias: irregular heart rhythms 2.Uncoordinated atrial and ventricular contractions 3.Fibrillation: rapid, irregular contractions; useless for pumping blood •Defective SA node may result in •Ectopic focus: abnormal pacemaker takes over •If AV node takes over, there will be a junctional rhythm (40–60 bpm) •Defective AV node may result in •Partial or total heart block •Few or no impulses from SA node reach the ventricles •Tachycardia: abnormally fast heart rate (>100 bpm) •If persistent, may lead to fibrillation •Bradycardia: heart rate slower than 60 bpm •May result in grossly inadequate blood circulation •May be desirable result of endurance training

Angina pectoris •Thoracic pain caused by a fleeting deficiency in blood delivery to the myocardium •Cells are weakened •Myocardial infarction (heart attack) •Prolonged coronary blockage •Areas of cell death are repaired with noncontractile scar tissue Congestive Heart failure or CHF Progressive condition where the CO is so low that blood circulation is inadequate to meet tissue needs •Caused by •Coronary atherosclerosis •Persistent high blood pressure •Multiple myocardial infarcts •Dilated cardiomyopathy (DCM)

Age related change to heart Sclerosis and thickening of valve flaps •Decline in cardiac reserve •Fibrosis of cardiac muscle •Atherosclerosis