The Circulatory System

• The circulatory system consists of the cardiovascular system (heart and blood vessels) and the circulatory system (heart, blood vessels, and blood)
• The circulatory system transports oxygen, carbon dioxide, nutrients, wastes, hormones, and stem cells.
• The circulatory system protects the body via the immune system and blood clotting.
• The circulatory system regulates fluid balance, pH, and temperature.
• Adults have 4 to 6 L of blood that is composed of plasma and formed elements.
• Blood is slightly warmer than the body's core temperature (100.4°F / 38°C)
• Blood color is dark red when oxygen is absent and bright red when bound to RBCs.
• The normal pH range of blood is 7.35-7.45
• Blood is denser (heavier) than water.
• Plasma makes up about 55% of the blood
• White blood cells and platelets make up about 4% of the blood
• Red blood cells make up about 41% of the blood
• During Centrifugation heaviest components of blood settle to bottom of tube, these are Erythrocytes/RBCs
• Hematocrit (Hct) is the packed cell value, the percentage of whole blood occupied by RBCs.
• Buffy coat is the narrow band of white blood cells and platelets.
• Plasma is the clear, yellow fluid on top of the tube after centrifugation.

Blood Plasma

• Blood plasma is the liquid portion of blood which contains proteins, wastes, nutrients, gases, and electrolytes.
• Albumin transports substances and influences blood viscosity and osmolarity.
• Globulins (antibodies) are antibodies secreted to combat pathogens in specialized immune responses.
• Fibrinogen is a component of blood clots.
• Wastes are nitrogenous wastes (urea).
• Nutrients include sugars, fats, amino acids, vitamins, and minerals.
• Gases dissolved include oxygen (O2), carbon dioxide (CO2), and nitrogen.
• Electrolytes include K+, Cl-, Mg+, Ca2+, and Na+.
• Serum is the remaining fluid when blood is allowed to coagulate (clot) and solids are removed, it is identical to plasma except for the absence of fibrinogen (clotting proteins).

Hematopoiesis

• Hematopoiesis is the production of blood (plasma and formed elements).
• Billions of platelets, RBCs, and WBCs must be made each day.
• Hematopoietic tissues produce all other formed elements in bone marrow.
• Hematopoietic stem cells (HSCs) are multipotent stem cells in bone marrow that give rise to all formed elements and must continue creating new cells throughout lifetime.

Erythrocytes

• Erythrocytes are red blood cells which carry oxygen from lungs to tissues and CO2 from tissues to lungs.
• Erythrocytes are designed to maximize gas exchange and transport and consist mostly of hemoglobin to carry gases.
• Erythrocytes lose nearly all organelles during development, including the nucleus
• Erythrocytes have no mitochondria making them use O₂ for energy
• Each hemoglobin protein consists of four protein subunits (globins) and four heme groups.
• Heme is a respiratory pigment that turns red when binds O₂.
• The iron atom (Fe) at core binds O₂
• There are four O₂ binding sites per Hb

Erythropoiesis

• Erythropoiesis is RBC production from hematopoietic stem cells (HSCs) in bone marrow.
• 1 million RBCs are produced per second. Average life span of about 120 days.
• Erythropoiesis is stimulated by erythropoietin (EPO) produced mainly by kidneys.
• Sufficient iron (Fe) from diet, vitamin B12, folic acid, vitamin C, and copper are required.
• Erythropoiesis is controlled by negative feedback loop.
• Polycythemia is an excess of RBCs.
  • Primary polycythemia is due to cancer in erythropoietic cell line in bone marrow.
  • Secondary polycythemia is due to dehydration, smoking, air pollution, and excessive aerobic exercise.
• Anemia is a deficiency of RBCs or hemoglobin.
  • Hemorrhagic anemias: are caused by excessive bleeding.
  • Hemolytic anemias: excessive RBC destruction.
  • Other causes of anemia include inadequate erythropoiesis, pernicious anemia, iron deficiency, aplastic anemia, and sickle-cell anemia.
  • Pernicious anemia: inadequate Vitamin B12 absorption because of reduced production of intrinsic factor by stomach.

Blood Types

• Blood types are based on interactions between antigens and antibodies.
• Antigens (Ag) are genetically unique molecules that occur on the surface of all cells so that our body can distinguish its own cells (self) from foreign materials (non-self).
• Antibodies (Anti-) are proteins that are secreted as part of a specific immune response whenever a foreign antigen is detected and bind to the antigens and mark them for destruction.
• Blood types are determined by the presence or absence of antigens on RBCs, and RBCs can have A antigen, B antigen, both A and B antigens, or neither.
  • Type A blood has the presence of A antigen
  • Type B blood has the presence of B antigen
  • Type AB blood has the presence of A & B antigens
  • Type O blood has no antigens present
• Blood plasma contains antibodies opposite of the antigens to.
• In Hemagglutination assay, clumping (agglutination) of red blood cells is a positive reaction.
  • Type A blood will react with anti-A serum
  • Type B blood will react with anti-B serum
  • Type O blood will not react with either
• Type O- is commonly known as the “universal donor" because there is no antigen A or antigen B on RBCs, meaning there are no antigens for the antibodies from donor blood to attack.
• Type AB+ is commonly known as the “universal recipient” because there are no anti-A or anti-B antibodies in plasma, meaning no antibodies will attack.

Leukocytes

• Leukocytes are white blood cells (WBCs)
• Leukocytes travel in blood to tissues to combat pathogens and foreign substances and play a role in responding to tissue damage.
• Granulocytes: include neutrophils, eosinophils, and basophils
• Agranulocytes: include lymphocytes and monocytes.

Leukocytes Granulocytes

• Neutrophils are the most abundant (60-70%) WBC, have a 3-5 lobed nucleus, and granules in cytoplasm, and aggressively phagocytize bacteria.
• Eosinophils are 2-4% of total WBCs, have red/orange granules in cytoplasm and respond to parasitic infections and dispose of allergens.
• Basophils are the least abundant (<1%), have many dark violet granules in cytoplasm and release histamine (vasodilator) and heparin.

Leukocytes Agranulocytes

• Lymphocytes account for 25-33% of total WBCS, have a large, dark nucleus, and little cytoplasm.
  • T cells directly attack infected or abnormal cells.
  • B cells become plasma cells that produce antibodies.
• Monocytes account for 3-8% of total WBCs, have a horseshoe-shaped or kidney-shaped nucleus, and are the largest WBC.
  • Monocytes become macrophages that phagocytize microbes and cellular debris.
• Platelets (thrombocytes) are small fragments of megakaryocyte cells
• Platelets Secrete clotting factors to promote blood clotting, stick together to help seal breaks in injured blood vessels, and can dissolve blood clots that are no longer needed

Hemostasis

• Hemostasis is the cessation of bleeding.
  • Stops potentially fatal leaks.
• Vascular spasm: Blood vessel walls rapidly constrict to reduce blood loss.
• Platelet plug formation: Platelets stick to injured endothelial cells and each other to loosely block injury.
• Coagulation: Fibrinogen protein in blood is converted to sticky fibrin, which forms clot of platelets and blood cells.
• There are two pathways to coagulation: intrinsic and extrinsic mechanisms.
  • The intrinsic mechanism is the reaction pathway that uses clotting factors that are within the blood itself.
  • The extrinsic mechanism is initiated by clotting factors that are released by the damaged blood vessel or nearby tissues.
  • Both pathways will eventually arrive to activate Factor X.
• In the presence of Ca2+, factor X combines with factor III and produces the enzyme prothrombin activator.
• Prothrombin activator converts a plasma protein called prothrombin to thrombin.
• Thrombin is an enzyme that will convert fibrinogen to fibrin.
• Fibrinolysis is the dissolution of a clot.
• Plasmin converts inactive plasminogen into active plasmin.
• Plasmin dissolves clot.
• Anticoagulants help prevent inappropriate coagulation and interferes with formation of prothrombin activator and Antithrombin deactivates thrombin before it can act on fibrinogen.

Pulmonary and Systemic Circuits

• Pulmonary circuit: right side of heart
  • Oxygen-poor blood arrives in right side of heart from inferior and superior venae cavae
  • Blood sent to lungs via pulmonary trunk for gas exchange and back to heart
• Systemic circuit: left side of heart
  • Fully oxygenated blood arrives in left side of heart from lungs via pulmonary veins
  • Oxygenated blood sent to all organs of the body via aorta and returned to the heart

The Pericardium

• The Pericardium is a double-walled sac that encloses the heart
• Allows heart to beat without friction, provides room to expand, yet resists excessive expansion
  • Parietal layer: lines fibrous pericardium
  • Visceral layer: covers heart wall
  • Pericardial cavity: space between two layers, contains pericardial fluid
• Structures of the heart wall
  • Epicardium (aka visceral layer of serous pericardium): serous membrane covering heart, contains some adipose tissue
  • Myocardium: layer of cardiac muscle, thickness proportional to workload, left ventricle thickest
  • Endocardium: smooth inner lining of heart and blood vessels
• The four heart chambers are atria and ventricals
  • Atria: superior chambers, receives blood returning to heart, and pump blood to ventricles
    • Right Atrium: receives DO2 from body
    • Left Atrium: receives O2 from lungs
  • Ventricles: inferior chambers that pump blood into arteries
    • Right Ventricle: goes to pulmonary trunk

Heart Valves

• Atrioventricular (AV) valves: control blood flow between atria and ventricles
  • Right AV/tricuspid valve has three cusps
  • Left AV/mitral/bicuspid valve has two cusps
• Semilunar valves: control flow from ventricles into great arteries
  • Pulmonary semilunar valve: opening between right ventricle and pulmonary trunk
  • Aortic semilunar valve: opening between left ventricle and aorta

Blood Flow Through the Chambers

• Blood flow goes from SVC, IVC, CS → Right Atrium → Right AV Valve → Right Ventricle → Pulmonary Valve → Pulmonary Trunk → Pulmonary Arteries
• From the lungs, blood flow goes from Pulmonary Veins → Left Atrium → Left AV Valve → Left Ventricle → Aortic Valve → Aorta → Organs of body
• The heart itself needs oxygen and nutrients.
  • Oxygen-rich blood is delivered to the heart with left & right coronary arteries branching off the aorta
• The structure of cardiac muscle is found only in the heart wall.
  • Cardiac muscle has short, branched, thick cells, and is under involuntary control.
  • Cardiac muscle Contains intercalated discs with cell junctions that join cardiomyocytes together and allow ions to flow between cells.

Cardiac Conduction System

• Sinuatrial (SA) node: pacemaker, in right atrium; initiates heartbeat
• ectopic focus: a region of spontaneous firing other than the SA node if it is damaged (usually AV node)
• Signals spread throughout atria
• Atrioventricular (AV) node: near the right AV valve at lower end of interatrial septum, spreads signal to ventricles
• Atrioventricular (AV) bundle (bundle of His): carries signal away from AV node, forks into right and left bundle branches
• Purkinje fibers: spread signal thereabout ventricles

Stimulation of the Myocardium

• Depolarization phase: very rapid depolarization
  • Stimulus opens voltage-regulated Na+ gates where Na+ rushes in, and membrane depolarizes rapidly (peak is at +30 mV) Na+ gates close quickly
• Plateau phase: 200 to 250 ms, sustains contraction for expulsion of blood from heart
  • Voltage-gated slow Ca2+ channels open, and Ca2+ inflow triggers release of Ca2+ from sarcoplasmic reticulum (SR), and binds to troponin triggering contraction
• Repolarization phase: Ca2+ channels close, K+ channels open, rapid outflow of K+ returns cell to resting potential (-90 mV)

Electrocardiograms

• P wave: represents atrial depolarization when signals from SA node spread through atria
• QRS complex: represents ventricular depolarization when signals from AV node spread through ventricles
• T wave: represents ventricular repolarization when ventricles relax
• PR Interval: time it takes impulses to travel from atria to ventricles
• QT interval: time it takes ventricles to contract and relax
• Signal conduction runs through the AV node, before activating ventricles
• Duration of ventricular depolarization and is shorter during exercise
• Ventricular systole corresponds to plateau in myocardial action potential.
• Cardiac cycle: series of events that occur in the heart during one complete heartbeat
• Involves the contraction and relaxation of the heart chambers.
• Systole which is the contraction of heart chambers blood is ejected out
• Diastole is the relaxation of heart chambers and fills with blood
• Two primary heart sounds are generated during the cardiac cycle; first sound is heard when atrioventricular valves occur. The second sound is caused from semilunar valves.
• Ventricular Filling ventricles are relaxed and blood pours from atria into ventricles
  • End-diastolic volume (EDV:) max volume ventricles can hold is 130 mL
• Isovolumetric Contraction pressure ventricles enough to force
• Ventricular Ejection: ventricles to contract and increase from and to pulmonary trunk and aorta
  • Stroke volume (SV): blood ejected (70 mL)
  • Cardiac output - blood leaving (60 mL)
• Isovolumetric: heart valves are closed chamber cannot fill, so ventricular expand to start cycle
• Cardiac output (CO:) Volume ejected by each 10 min is CO CO = heart rate (HR) x stroke volume (SV)
• About 4 to 6 L/min at rest, increases to about 21 L/min during exercise for a fit person.
• Heart rhythm and contraction controlled in medulla.

Autonomic Nerves

• Cardioacceleratory which increases heart rate and contractility.
• Cardioinhibitory centers parasympathetic and vagus nerve.