BIO 3260 Midterm 2 Notes PDF

**Midterm 2 Notes and Study Questions** **Muscle Physiology** Types of Muscles - Muscle comprises largest group of tissues in the body - Three types of muscle - Skeletal muscle makes up muscular system - Cardiac muscle only found in the heart - Smooth muscle appears thro...

**Midterm 2 Notes and Study Questions** **Muscle Physiology** Types of Muscles - Muscle comprises largest group of tissues in the body - Three types of muscle - Skeletal muscle makes up muscular system - Cardiac muscle only found in the heart - Smooth muscle appears throughout body systems as components of hollow organs and tubes - Classified in two different ways - Striated vs. unstriated (structure) - Voluntary vs. involuntary (control) Muscle Function - Controlled muscle contraction allows: - Purposeful movement of the whole body or parts of the body - Manipulation of external objects - Propulsion of contents through various hollow internal organs - Emptying of contents of certain organs to external environment Structure of Skeletal Muscle - Muscle consists of a number of muscle fibres lying parallel to one another and held together by connective tissue - A single skeletal muscle cell is known as a muscle fibre - Multinucleated - Large, elongated and cylindrically shaped - Fibres usually extend entire length of muscle Skeletal Muscle Fibres - Myofibrils are contractile elements of a muscle fibre - Regular arrangements of thick and thin filaments - Thick filaments: myosin (protein) - Thin filaments: actin (protein) - Viewed microscopically, a myofibril displays alternating dark bands (the A bands) and light bands (the I bands), giving the appearance of striations Functional Unit - Found between two Z-lines (connects the thin filaments of two adjoining sarcomeres) - Regions of sarcomere: - A band: made up of thick filaments along with portions of thin filaments that overlap on both ends of thick filaments - H zone: lighter area within middle of A band where thin filaments do not reach - M line: extends vertically down middle of A band within centre of H-zone - I band: consists of remaining portion of thin filaments that do not project into A band Myosin - Component of thick filaments - Protein molecule consisting of two identical subunits shaped somewhat like a golf club - Tail ends intertwined around each other - Globular heads project from one end - Heads form cross bridges between thin and thick filaments - Cross bridge has two important sites critical to contractile process - Actin binding site - Myosin ATPase (ATP splitting) site Actin - Actin is the primary structural component of thin filaments: spherical in shape - Each actin molecule has special binding site for attachment with myosin cross bridge - Binding results in contraction of muscle fibre - Actin and myosin are often called contractile proteins - Neither one actually contracts - Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells Tropomyosin and Troponin - Tropomyosin: thread-like molecules that lie end-to-end alongside the groove of actin spiral - In this position, they cover actin sites, blocking the interaction that leads to muscle contraction - Troponin: made of three polypeptide units: - One binds to tropomyosin - One binds to actin - One can bind with Ca^2+^ - When not bound to Ca^2+^, troponin stabilizes tropomyosin in blocking the position over actin's cross bridge binding sites - When Ca^2=^ binds to troponin, tropomyosin moves away from the blocking position - With tropomyosin out of the way, actin and myosin bind and interact at cross bridges - Muscle contraction results Cross Bridge Cycle 1. Energized: ATP split by myosin ATPase; ADP and P~i~ remain attached to myosin; energy stored in cross bridge 2. Binding or Resting a. Binding: Ca^2+^ released on excitation; removes inhibitory influence from actin, enabling it to bind with cross bridge b. Resting: No excitation; no Ca^2+^ released; actin and myosin prevented from binding; no cross bridge cycle; muscle fibre remains at rest 3. Bending: Power stroke of cross bridge triggered on contact between myosin and actin; P~i~ released during and ADP released after power stroke 4. Detachment or Rigor Complex c. Detachment: Linkage between actin and myosin broken as fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original conformation; ATP hydrolyzed (cycle starts again at Step 1) d. Rigor Complex: If no fresh ATP available (after death), actin and myosin remain bound in rigor complex Rigor Mortis - "Stiffness of death" begins 3 to 4 hours after death and is complete in about 12 hours - Dead cells cannot make ATP, so actin and myosin, once bound, cannot detach Linkage of Motor Neurons and Skeletal Muscle Fibres - An action potential in a motor neuron propagates to skeletal muscle along efferent fibres - Axon terminals form a neuromuscular junction with muscle fibres - Axon terminal - Terminal Button - Motor end plate - Axon terminal of motor neuron forms neuromuscular junction with a single muscle cell - Signals are passed between nerve terminal and muscle fibre by means of neurotransmitter ACh - Released ACh binds to receptor sites on motor end plate of muscle cell membrane Acetylcholine (ACh) - Neurotransmitter - Carries action potential across synapse to muscle fibre Formation of an End Plate Potential - Binding triggers the opening of specific channels in motor end plate - Ion movements depolarize motor end plate, producing end plate potential - Local current flow between depolarized end plate and adjacent muscle cell membrane brings adjacent areas to threshold - Action potential is initiated and propagated throughout the muscle fibre Acetylcholinesterase and Acetylcholine Actvity - Acetylcholinesterase (AChE) inactivates ACh - Ends the end-plate potential and the action potential and the resultant contraction - Removes most ACh within a few milliseconds after its release Vulnerability of the Neuromuscular Junction - Neuromuscular junction is vulnerable to chemical agents and diseases - Black widow spider venom causes explosive release of ACh - Botulism toxin blocks release of ACh - Curare blocks release of ACh - Organophosphates prevent inactivation of ACh - Myasthenia gravis inactivates ACh receptor sites Excitation-Contraction Coupling - Series of events linking muscle excitation to muscle contraction - Muscles stimulated to contract with release of ACh - ACh is a neurotransmitter, a chemical that carries messages from your brain to your body through nerve cells; and excitatory neurotransmitter - ACh operates as a neurotransmitter in many parts of the body, but it is most commonly associated with the neuromuscular junction Spread of the Action Potential down the T-Tubules - At A band and I band, surface membrane dips to form a transverse tubule (T-tubule) - Rus perpendicular from the surface into the central portion of the muscle - Action potentials spread down T-tubules Calcium Release in Excitation-Contraction Coupling 1. ACh released by axon of motor neuron crosses cleft and binds to receptors/channels on motor end plate 2. Action potential generated in response to binding of ACh and subsequent end plate potential is propagated across surface membrane and down T-tubules of muscle cell 3. Action potential in T-tubule triggers Ca^2+^ release from sarcoplasmic reticulum 4. Calcium ions released from lateral sacs bind to troponin on actin filaments; leads to tropomyosin being physically moved aside to uncover cross bridge binding sites on actin 5. Myosin cross bridges attach to actin and bend, pulling actin filaments toward centre of sarcomere; powered by energy provided by ATP 6. Ca^2+^ actively taken up by sarcoplasmic reticulum (SR) when there is no longer local action potential Release of Calcium from Sarcoplasmic Reticulum - Modified endoplasmic reticulum - Consists of fine network of interconnected compartments that surround each myofibril - Not continuous but encircles myofibril throughout its length - Segments are wrapped around each A band and each I band Relaxation - Depends on reuptake of calcium ions into SR - AChE breaks down ACh at neuromuscular junction - Muscle fibre action potential stops - When local action potential is no longer present, calcium ions move back into SR Contractile Activity - Latent period: time delay between stimulation and the onset of contraction - Contraction time: time from onset of contraction until peak tension develops - Time varies depending on muscle fibre type Factors Affecting Muscle Strength - Sex (males have higher muscle mass due to testosterone) - Body weight - Age - Fitness - Muscle Type - Muscle cross-sectional area **Study Questions:** **Describe the macro- and microstructure of skeletal muscle that enables force development.** Muscles are made up of muscle fibres which lay parallel to each other. A single skeletal muscle cell is called a muscle fibre. It is multinucleated, cylindrical in shape and often extend the whole length of a muscle. Muscle fibres are held together by connective tissue. Muscle fibres are further broken down into myofibrils; the contractile elements of a muscle fibre. Myofibrils are composed of arranged thick and thin filaments. Thick filaments are made up of myosin molecules and thin filaments are made up of actin molecules. Myosin is a protein molecule that is shaped similar to a golf club. The tail ends intertwine around each other and have globular heads projecting from the ends. Actin is spherical in shape. Actin and myosin are often called contractile proteins even though they do not actually contract. The functional unit of the muscle is a sarcomere. Myofibrils are composed of many repeating sarcomeres, found between two Z-lines. Z-lines connect the thin filaments of two adjoining sarcomeres. Sarcomeres consist of many additional regions. The A band is made up of thick filaments along with portions of thin filaments that overlap at the end of the thick filaments. The H-zone is the lighter area in the middle of the A band where no thin filaments reach. The M-line extends vertically down the middle of the A band, in the centre of the H-zone. Finally, the I band consists of the remaining portions of thin filaments that do not project into the A band. **Describe the molecular basis for skeletal muscle contraction.** Skeletal muscle contraction occurs due to action of cross bridges formed by myosin and actin. There are two sites important to the contractile process; the actin binding site and the myosin ATPase site. Actin possesses a special binding site for attachment with the myosin cross bridge. Tropomyosin and troponin are also important molecules involved in the muscle contraction process. Tropomyosin is a thread-like molecule that lies along the groove of the actin spiral, covering the actin sites and therefore blocking the interaction necessary for muscle contraction. Troponin is a polypeptide made of three subunits; one binds to tropomyosin, one binds to actin and one binds to calcium ions. When troponin is not bound to calcium ions, it stabilizes tropomyosin in blocking the actin binding sites crucial in the cross bridge reaction. When calcium is bound to troponin, the tropomysin moves away from the binding site allowing actin and myosin to interact at cross bridges, resulting in muscle contraction. This is known as the cross bridge cycle. **Describe the processes of excitation-contraction coupling.** Excitation-contraction coupling is a series of events that link muscle excitation to muscle contraction. Muscles are stimulated to contract with the release of acetylcholine (ACh). Acetylecholine is an excitatory neurotransmitter, meaning it will cause an excitation rection at the motor end plate. At the I band and A band, the surface membrane dips to form a transverse tubule (T tubule). T tubules run perpendicular from the surface into the central portion of the muscle; action potentials spread down T tubules. Following the release of ACh, an action potential is generated by the binding of ACh to the motor end plate. This produces an endplate potential, which is then propagated down T tubules. This action potential triggers the release of calcium ions from the sarcoplasmic reticulum; a modified ER that consists of a network of compartments surrounding each myofibril. The released calcium ions bind to troponin on actin filaments, causing the actin binding sites to be exposed by the movement of tropomyosin. The myosin cross bridges then attach to the actin and bend; this pulls the actin filaments toward the centre of the sarcomere. Calcium is then taken up by the sarcoplasmic reticulum when there is no longer an action potential. The reuptake of calcium ions causes the tropomyosin to slip back into place, blocking the actin binding sites and ending contraction. Acetylcholinesterase (AChE) breaks down ACh at the neuromuscular junction to stop the action potential. **Which factors can affect muscle strength?** Muscle strength can be impacted by many factors including sex, body weight, age, fitness, muscle type and muscle cross-sectional area. **Cardiac Physiology** Three basic components of the circulatory system - Heart - Serves as pump that established the pressure gradient needed for blood to flow to tissues - Blood vessels - Passageways through which blood is distributed from heart to all parts of body and back to heart - Blood - Transport medium within which materials being transported are dissolved or suspended Pulmonary and System Circulation in Relation to the Heart - Pulmonary circulation: closed loop vessels carrying blood between heart and lungs - Systemic circulation: Circuit of vessels carrying blood between heart and other body systems - Positioned between two bony structures: sternum and vertebrae How big is your heart? - Size of the heart is approximately the size of your fist Dextrocardia - Heart positioned slightly to the right side of the chest instead of the left - Less than 1% of the population has this condition; about 1 in every 8,000 to 25,000 Comparison of Right and Left Pumps - Both sides of the heart simultaneously pump equal amounts of blood - Pulmonary circuit is low pressure, low resistance - Systemic circuit is high pressure, high resistance - When pressure is greater behind the valve, it opens - When pressure is greater in front of the valve it closes; it does not open in the opposite direction (one-way valve) The Heart Walls - Consists of three distinct layers - Endothelium (endocardium) - Thin inner tissue - Epithelial tissue that lines entire circulatory system - Myocardium - Middle layer - Composed of cardiac muscle - Constitutes bulk of heart wall - Epicardium - Thin external layer that covers the heart The Pericardial Sac - Heart is enclosed by pericardial sac - Pericardial sac has two layers - Tough fibrous covering - Secretory lining - Secretes pericardial fluid - Provides lubrication to prevent friction between pericardial layers - Pericarditis - Inflammation of pericardial sac - Myocarditis - Inflammation in heart muscle Electrical Activity of the Heart - Heart beats rhythmically as a result of action potentials it generates by itself (autorhythmicity) - Two specialized type of cardiac muscle cells - Contractile cells - 99% of cardiac muscle cells - Do mechanical work of pumping - Normally do not initiate their own action potentials - Autorhythmic cells - Do not contract - Specialized for initiation and conducting action potentials responsible for contraction of working cells Sinoatrial Node - Locations of noncontractile cells capable of autorhythmicity - Sinoatrial node (SA node) - Specialized region in right atrial wall near opening of superior vena cava - Pacemaker of the heart - Atrioventricular node (AV node) - Small bundle of specialized cardiac cells located at base of right atrium near septum - Locations - Bundle of His (AV bundle) - Cells originate at AV node and enter interventricular septum - Divides to form right and left bundle branches, which travel down septum, curve around tip of ventricular chambers, travel back toward atria along outer walls - Purkinje fibres - Small, terminal fibres that extend from bundle of His and spread throughout ventricular myocardium Cardiac Muscle Fibres - Interconnected by intercalated discs and form functional syncytia - Within intercalated discs: two kinds of membrane junctions - Desmosomes -- mechanically important - Gap junctions -- electrically important - Bundles of cardiac muscle are arranges spirally around the ventricle; when they contract they "wring" blood from the apex to the base where the major arteries exit Review - The sympathetic nervous system (SNS, stress) releases the hormones (catecholamines -- epinephrine and norepinephrine) to accelerate the heart rate - The parasympathetic nervous system (PNS, relaxation after stress) releases the hormone acetylcholine to slow the heart rate The ECG - Record of overall spread of electrical activity through heart - Represents recording parts of electrical activity induced in body fluids by cardiac impulse that reaches body surface - Not direct recording of actual electrical activity of heart - Recording of overall spread of activity throughout the heart during depolarization and repolarization - Not a recording of a single action potential in a single cell at a single point in time - Comparisons in voltage detected by electrodes at two different point s on body surface, not the actual potential The ECG Record - Three distinct wave forms - The P wave represents atrial depolarization - The QRS complex represents ventricular depolarization (atria repolarize simultaneously) - The T wave represents ventricular repolarization Abnormalities in Rate - Tachycardia: A rapid heart rate of more than 100 beats per minute - Bradycardia: a slow heart rate of less than 60 beats per minutes Development of Atherosclerosis - Progressive, degenerative arterial disease that leads to occlusion of vessel - Atherosclerotic plaque consists of a lipid-rich core covered by abnormal overgrowth of smooth muscle cells, topped with connective tissue - Starts with injury to the blood vessel, which triggers an inflammatory response that sets the stage for plaque buildup Thromboembolism and Other Complications of Atherosclerosis - Most serious consequences involve damage to the vessels of the brain and heart - Prime cause of stroke in the brain and myocardial ischemia in the heart - Potential complications of coronary atherosclerosis - Thromboembolism - Heart attack Heart Attack vs. Cardiac Arrest - Heart attack - Myocardial infarction - Part of the heart muscle isn't receiving blood (oxygen supply) - Painful - Cardiac arrest - Autorhythmic cells don't function - Patient unconscious - Cardiopulmonary resuscitation (CPR) - 100-120 compressions/min Blood Pressure - Blood pressure is recorded as two numbers - Systolic blood pressure: indicates how much pressure your blood is exerting against your artery walls when the heart contracts - Diastolic blood pressure: indicates how much pressure your blood is exerting against your artey walls while the heart muscle is resting between contractions - The Mean Arterial Pressure (MAP) calculates mean arterial pressure from measured systolic and diastolic blood pressure values **Study Questions** **Locate the heart anatomically.** The heart is located in the human chest, pushed slightly towards the left side of the chest by the left lung. It is positioned between the sternum and the vertebrae. It is approximately the size of your fist. **Describe the path blood takes through the cardiovascular system.** There are two types of circulation through the cardiovascular system. Pulmonary circulation refers to the closed loop of vessels that carry blood between the heart and the lungs. This circulation is important for the reoxygenation of the blood. Systemic circulation is the circuit of vessels that carry blood between the heart and other body systems such as the muscles, the kidneys, the digestive tract and the brain. **Explain the movement of blood through the heart.** Oxygen poor blood returns from other body systems through the vena cava (superior: returns blood from head and upper limbs, inferior: returns blood from trunk and legs). This blood enters the right atrium of the heart. The blood flows through the right atrioventricular valve into the right ventricle. With some force, the blood is pumped through the pulmonary semilunar valve to the right and left pulmonary arteries. It is then transported to the lungs to be re-oxygenated. The re-oxygenated blood returns from the lungs through the left and right pulmonary veins (from left and right lung respectively). The blood enters the left atrium of the heart. It then passes through the left atrioventricular valve and into the left ventricle. With force, the blood is then pushed through the aortic semilunar valve to the aorta where is is then transported to the rest of the body to carry out systemic circulation. **Discuss how the contraction of cardiac muscle is initiated by electrical activity through nodal cells.** The heart is autorhythmic as a result of the action potentials it generates by itself. The heart has two specialized kinds of cardiac muscle cells; contractile cells and autorhythmic cells. Contractile cells make up 99% of cardiac muscle cells and do the mechanical work associated with pumping the blood. These cells do not create their own action potentials. However, autorhythmic cells do not contract and are specialized for initiating and conducting action potentials to contract the working cells. These cells are found in the sinoatrial node (SA node) and the atrioventricular node (AV node). The SA node is a specialized region in the right atrial wall near the opening of the superior vena cava that is known as the pacemaker of the heart. It initiates all heartbeats and controls the heart rate. The AV node is the small bundle of specialized cells at the base of the right atrium near the septum. The Bundle of His (atrioventricular bundle) originates in the AV node and enters the septum. It divides to form right and left branches that travel down the septum and curve around the tip of the ventricular chambers and travel back towards the atria along the outer walls of the ventricles. The Purkinje fibres are small terminal fibres that extend from the Bundle of His through the ventricular myocardium. All of these structures are essential for ensuring the heart beats with a proper rhythm. **Describe the major steps in the development of atherosclerosis and the resultant problems this causes for the heart.** Atherosclerosis is a degenerative arterial disease that leads to the complete occlusion of vessels. An atherosclerotic plaque consists of a lipid-rich core covered by abnormal overgrowth of smooth muscle cells, topped with connective tissue. This condition begins with an injury to the blood vessel. This injury triggers an inflammatory response, which allows for the possibility of plaque buildup. The most severe consequences of this disease involve damage to the vessels of the brain and heart. Atherosclerosis is the prime cause of stroke in the brain and myocardial ischemia in the heart. Potential complications of coronary atherosclerosis are thromboembolisms and heart attacks. An individual often requires a stent or a bypass surgery in order to recover from this condition. **Describe how protein intake can affect cardiovascular function in rats.** Lower protein intake can increase the MAP and HR of rats. This means adequate protein is necessary for proper cardiovascular health. **Vascular Physiology** Three basic components of the circulatory system - Heart - Serves as pump that establishes the pressure gradient needed for blood to flow to tissues - Blood vessels - Passageways through which blood is distributed from heart to all parts of body and back to heart - Blood - Transport medium within which materials being transported are dissolved or suspended Blood - Blood is constantly reconditioned so that the composition remains relatively constant - Reconditioning organs receive more blood than needed for metabolic needs - Lungs (O~2~ and CO~2~ exchange) - Kidneys (blood volume and electrolyte composition - Skin (temperature) - Blood flow to other organs can be adjusted according to metabolic needs - The brain can least tolerate disrupted supply; neither can the heart Distribution of Cardiac Output at Rest - Right side of heart - Pumps 100% of blood to lungs - Left side of the heart - 21% digestive system - 6% Liver - Hepatic portal system between digestive system and liver - 20% kidneys - 9% skin - 13% brain - 3% heart muscle - 15% skeletal muscle - 5% bone - 8% other The Vascular Tree - Arteries - Carry blood from heart to tissue - Arterioles - Smaller branches of arteries - Capillaries - Smaller branches of arterioles - Smallest of vessels across which all exchanges are made with surrounding cells - Venules - Formed when capillaries rejoin - Return blood to heart - Veins - Formed when venules merge - Return blood to heart Blood Vessels - Blood vessel walls are composed of alternating layers of connective tissue, smooth muscle and epithelial cells Arterioles - Major resistance vessels radius supplying individual organs can be adjusted independently to - Distribute cardiac output among systemic organs, depending on body's momentary needs - Help regulate arterial blood pressure Capillaries - Thin-walled, small radius, extensively branched - Sites of exchange between blood and surrounding tissues - Maximized surface area and minimized diffusion distance - No carrier-mediated transport system across capillaries - Diffusion distances - Enhanced surface area for diffusion - Slow velocity through capillaries Slow Velocity of Flow Through Capillaries - Velocity of blood flow through capillaries is relatively slow - Provides adequate exchange time - Two types of passive exchanges - Diffusion - Bulk flow Capillaries Under Resting Conditions - Many capillaries are not open - Capillaries surrounded by precapillary sphincters - Contraction of sphincters reduces blood flowing into capillaries in an organ; relaxation of sphincters has opposite effect - Metarteriole - Runs between and arteriole and a venule Independent Exchange of Individual Solutes Down their Own Concentration Gradients Across the Capillary Wall - Solutes cross primarily by diffusion down concentration gradients The Lymphatic System - Extensive network of one way vessels - Provides accessory route by which fluid can be returned from interstitial spaces to the blood - Initial lymphatics - Small, blind-ended terminal lymph vessels - Permeate almost every tissue of the body - Fluid pressure on the outside of the vessel pushes the endothelial cell's free edge inward, permitting entrance of interstitial fluid (now lymph) - Fluid pressure on the inside of the vessel forces the overlapping edges together s that lymph cannot escape Blood Flow and the Pressure Gradient - Rate of blood flow - Depends on pressure gradient - Depends on resistance of blood vessels - The pressure gradient is the pressure difference between the beginning and end of a vessel - Blood flows from an area of higher pressure to an area of lower pressure, down a pressure gradient - Pressure drops due to friction as blood flows throughout a vessel's length - Resistance is dependent on - Blood viscosity, vessel length, vessel radius Vasoconstriction and Vasodilation - Mechanisms involved in adjusting arteriolar resistance - Vasoconstriction - The narrowing of a vessel - Caused by: increased myogenic activity, oxygen, endothelin, sympathetic stimulation; decreased carbon dioxide and other metabolites; vasopressin, angiotensin II, cold - Vasodilation - The enlargement in circumference and radius of a vessel - Results from relaxation of smooth muscle layer - Leads to decreased resistance and increased flow through that vessel - Cause by: decreased myogenic activity, oxygen, sympathetic stimulation; increased carbon dioxide and other metabolites, nitric oxide; histamine release, heat Local Vasoactive Mediators - Endothelial cells - Release chemical mediators that play key role in locally regulating arteriolar calibre - Release locally acting chemical messengers in response to chemical changes in their environment - Among best studied local vasoactive mediators in nitric oxide (NO) The Medullary Cardiovascular Control Centre - Located in medulla of brain stem - Influence of epinephrine and norepinephrine - Sympathetic stimulation of the adrenal medulla - Influence of vasopressin and angiotensin II - Play role in maintaining body's fluid balance - Both are potent vasoconstrictors The Baroreceptor Reflex - Short term control adjustments - Occur within seconds - Adjustments made by alterations in cardiac output and total peripheral resistance - Mediated by means of autonomic nervous system influences on heart, veins and arterioles - Long term control adjustments - Require minutes to days - Involve adjusting total blood volume by restoring normal salt and water balance through mechanisms that regulate urine output and thirst - Arterial baroreceptors found in carotid arteries and aortic arch Components of the Blood - Plasma - Erythrocytes - Red blood cells - Important in O~2~ transport - Leukocytes - White blood cells - Immune system's mobile defence units - Platelets - Cell fragments - Important in haemostasis Plasma - Plasma is 90% water - Three groups of plasma proteins - Albumins - Most abundant plasma proteins - Globulins - Three subclasses: alpha, beta, and gamma - Fibrinogen - Key factor in blood clotting Erythrocytes -- Red Blood Cells (RBCs) - Contain no nucleus, organelles or ribosomes - Structure is well suited to maintain function of O~2~ transport in the blood - Biconcave discs - Provides larger surface area for diffusion of O~2~ across the membrane - Thinness of cell enables O~2~ to diffuse rapidly between the exterior and innermost regions of the cell - Flexible membrane - Allows RBCs to travel through narrow capillaries without rupturing in the process Haemoglobin - Found only in red blood cells - Pigment containing iron - Appears reddish when oxygenated - Appears bluish when deoxygenated - Molecule consists of two parts - Globin portion - Protein composed of four highly folded polypeptide chains - Each is bound to one of the polypeptides Erythrocytes' Short Life Span - RBCs survive about 120 days - Spleen removes most old erythrocytes from circulation - Erythropoiesis occurs in red bone marrow - Pluripotent stem cels in red bone marrow differentiate into the different types of blood cells - Erythropoietin - A hormone secreted by the kidneys that stimulates RBC production - Synthetic version available Erythropoiesis - The kidneys detect reduced oxygen carrying capacity of the blood - When less oxygen is delivered to the kidneys, they secrete the hormone erythropoietin into the blood - Erythropoietin stimulates erythropoiesis (erythrocyte production) by the bone marrow - The additional circulating erythrocytes increase the oxygen carrying capacity of the blood - Increased oxygen carrying capacity relieves the initial stimulus that triggered erythropoietin secretion ABO blood types - Blood types depend on the surface antigens on erythrocytes: - Type A blood contains A antigens - Type B blood contains B antigens - Type AB blood has both A and B antigens - Type O blood has neither A nor B antigens - Antibodies against foreign RBC antigens appear in human plasma after six months of age RH Blood Types - People who have the Rh factor have Rh-positive blood - People lacking the Rh factor are Rh-negative - No naturally occurring antibodies develop against the Rh factor - Anti-Rh antibodies are produced only by Rh-negative people if exposed to Rh-positive blood Leukocytes - White blood cels (WBCs)/immune cells - Neutrophils - Eosinophils - Basophils - Monocytes - Lymphocytes Platelets - Called thrombocytes - Cell fragments shed from megakaryocytes - Lack nuclei - Have organelles and cytosolic enzymes for generating energy and synthesizing secretory products - High concentrations of actin and myosin - Remain functional for an average of 10 days - Removed from circulation by tissue macrophages - Thrombopoietin - Hormone produced by the liver increases number of megakaryocytes, increasing platelet production Haemostasis - Haemostasis prevents blood loss from a broken blood vessel - Involves three major steps - Vascular stream - Reduces blood flow through a damaged vessel - Formation of a platelet plug - Platelets aggregate on contact with exposed collagen in damaged wall of vessel - Platelets release ADP, causing surface of nearby circulating platelets to become sticky and adhere to first layer of aggregated platelets - Blood coagulation (clotting) - Transformation of blood from liquid into a solid gel **Study Questions** **Compare and contrast the structure of the major classes of blood vessels.** There are many different classes of blood vessels, all with their own important function. Arteries carry the oxygenated blood from the heart to the tissues. They are the largest type of blood vessel and include the aorta and pulmonary artery. Arterioles are smaller branches of the arteries. They provide blood supply to various tissues. They are the midsized blood vessels that carry oxygenated blood. Capillaries are smaller branches of arterioles. They are the smallest type of vessel. Capillaries are the location of exchanges made with surrounding cells. They are surrounded by precapillary sphincters; their contraction reduces blood flow into capillaries of an organ, relaxation has the opposite effect. Venules are formed when capillaries rejoin. They are the midsized blood vessel that carry deoxygenated blood. Veins are formed when venules merge and carry blood back to the heart. They are the largest blood vessels that carry deoxygenated blood. **Explain how arteriolar radius can change and what impact this would have on blood flow.** Arteriolar radius is capable of changing. These changes are called vasoconstriction and vasodilation. Vasoconstriction refers to the narrowing of blood vessels. This results from increased contraction of the smooth muscle cells in the arteriolar wall. Therefore, increased resistance and decreased flow is observed through the vessel. Vasodilation refers to the enlargement of the arteriolar radius. This results from decreased contraction of the smooth muscle cells of the arteriolar wall. Therefore, decreased resistance and increased flow is observed through the vessel. Endothelial cells play a role in regulating arteriolar radius by releasing chemical messengers such as NO. The medulla also contributes to cardiovascular control with the influence of epinephrine, norepinephrine, vasopressin and angiotensin II. These play a role in the baroreceptor reflex, which ensures the proper maintenance of blood pressure regardless of vasoconstriction and vasodilation, both short and long term. **Describe the characteristics that make capillaries an optimal site for exchange.** Capillaries are very thin walled and extensively branched blood vessels. They allow for the exchange of materials between the blood and surrounding tissues. Capillaries are optimal exchange sites due to their maximized surface area and minimized distance necessary for diffusion. Additionally, blood flow is slow through the capillaries which allows for adequate time to exchange materials passively. There is no carrier-mediated transport necessary, except in the brain, which also aids in the optimal conditions for exchange. **Describe the need for the lymphatic system.** The lymphatic system is a network of one-way vessels that provide an accessory route by which fluid can be returned from the interstitial spaces to the blood. Initial lymphatics are small, blind-ended terminal lymph vessels that permeate almost every body tissue. Fluid pressure on the outside of the vessel pushes the endothelial cells inward, permitting entrance of interstitial fluid, now called lymph. Fluid pressure on the inside of the vessel forces the overlapping edges together so the lymph cannot escape. **Defence Mechanisms** Immune System Basics - Primary organs: where lymphocytes are formed and mature - Bone marrow - Thymus - Secondary Organs: Series of filters that monitor the contents of the extracellular fluids (lymph, tissue fluid, blood) - Lymph nodes - Spleen - Tonsils - Mucosa associated lymphoid tissue (MALT) - Important for defence against disease causing organisms (e.g. bacteria, viruses), malfunctioning cells and foreign materials - Also important for brain development and homeostasis in adulthood Primary and Secondary Lines of Defence - Primary: barriers that keep foreign material out (innate immunity) - Skin - Saliva - Mucus and cilia - Stomach acid - Secondary: mechanisms targeting foreign material that enters the body (innate and adaptive immunity) - White blood cells (WBCs) - Cytokines Innate Immunity - Surface defences - Skin - Hair - Mucus - Internal Defences - Mast cells and basophils (inflammatory response) - Natural killer cells - Complement system - Phagocytes - Monocytes, neutrophils, macrophages - Cells/proteins/barriers that are always present - Non-specific and act quickly Adaptive Immunity - T lymphocytes - Effector and memory cells - Antigen-presenting cells - B lymphocytes - Effector and memory cells - Activated to combat pathogens that evade/overcome the innate immune system - Highly specific: activation and proliferation of cells against the specific pathogen - Slower - B cells: stimulated by an antigen, differentiate into plasma (effector) cells to produce neutralizing antibodies (mark for phagocyte destruction) - T cells: recognize fragments displayed by antigen presenting cells The Inflammatory Response - Activated immune cells produce cytokines - Cytokines: - Small proteins produced and secreted by immune cells (and other cell types) - Act through receptors to modulate the immune response, cell growth and differentiation, etc. Psychoneuroimmunology - Field examining the interactions between the nervous, immune (and endocrine) systems - Brain previously considered an "immunoprivileged organ" - CNS considered inaccessible to the immune system (Blood-Brain Barrier) - Absence of lymphatic system - Transplantation of tissue (tumor or fetal) into the brain was not rejected (studies from 1920s/1930s) - Today, brain is considered "immunologically unique" How do the CNS and Immune System Communicate? - Transport of immune system messengers (cytokines) from the periphery into the brain - Cytokines activate afferent nerves (e.g. vagus) - Circumventricular organs - Regions in the brain where the capillary bed does not form a BBB (around third and fourth ventricles), allowing for CNS/periphery communication - Share a common language: receptors and ligands - Peptides, steroids, cytokines, etc. are immunologically active Neuroimmunology: Areas of Study - Brain -- pathological immune interactions with CNS - Brain -- microglia and neuron maintenance - Lymphatic vessels -- immune-CNS interactions in homeostasis - Brain and spinal cord -- protective immunity in injury and disease - Cervical lymph nodes and spleen -- nervous system interaction with secondary immune organs - Gut immune system-CNS interactions and microbiota Neuroimmune System: Microglia - Permanent resident immune cells of the CNS - Located throughout the brain - "Police officers" of the brain -- survey brain and respond to injury, trauma, disease - Never really rest; constantly sampling their environment - Monitor synapses - Example: raise mice in dark, microglia make fewer contact with neurons in the visual cortex Role of Neuroimmune System in Brain Development - During brain development, microglia prune excess synapses - Aberrant synaptic pruning linked to developmental disorders - Schizophrenia - Autism Spectrum Disorder (ASD) - Neuroimmune system also important for: neurogenesis, neuronal migration, synaptogenesis, angiogenesis, myelination, apoptosis Impacts of Early Immune Activation - Because the neuroimmune system is critical for brain development, disturbances to this system may result in alterations in brain development - Maternal immune activation can impact brain development (mechanism currently unknown) - Examples: - 1957 Influenza epidemic - Maternal influenza infection increases the risk of schizophrenia in the offspring - 1964 rubella pandemic - Increased risk of autism and schizophrenia - Maternal immune activation (MIA) model: - Poly(I:C) -- mimics a viral infection - Lipopolysaccharide (LPS) -- mimics a bacterial infection - Effects - Behavioural - Abnormal social behaviour, increased repetitive behaviours, increased anxiety - Brain: - Decreased cortical thickness and hippocampal volume - MIA may act as disease primer and when combined with other factors (genetics, environment, later life infections, etc.) results in disease **Study Questions** **What are the primary and secondary lines of defence?** The primary lines of defence are the barriers that keep foreign material out. These are related to innate immunity. Examples include the skin, saliva, mucus and cilia and stomach acid. These defences act quickly and are non-specific. The secondary lines or defence are the mechanisms targeting foreign material that enters the body. These are related to both innate and adaptive immunity. Examples include white blood cells and cytokines. These defences are highly specific and act slower. **Which cells belong to innate vs. adaptive immunity?** Cells that belong to innate immunity are: - Mast cells and basophils (important in the inflammatory response) - Natural killer cells - The complement system - Phagocytes - Monocytes - Neutrophils - Macrophages Cells that belong to adaptive immunity are: - T-lymphocytes - Antigen -presenting cells - B lymphocytes **What are cytokines?** Cytokines are small proteins that are produced and secreted by immune cells; they can also be secreted by other types of cells. Cytokines act through receptors to modulate immune response, cell growth and differentiation. **Can the nervous system communicate with the immune system? If so, how?** Yes, the nervous system and the immune system can communicate. Immune system messengers (cytokines) are transported from the periphery into the brain. The cytokines activate afferent nerves, such as the vagus nerve. This communication occurs in circumventricular organs; regions of the brain where the capillary bed does not form a BBB (around third and fourth ventricles). The brain and the immune system share a common language of ligands and receptors. Peptides, steroids and cytokines are also immunologically active. **What is MIA?** Maternal Immune Activation (MIA) refers to the effect of illness in a mother during childbearing on the development of the child. Since the neuroimmune system is critical in brain development, disturbances may alter brain development in the fetus. Examples of this include following the 1957 influenza epidemic and 1964 rubella pandemic which both increased the risk of schizophrenia in the offspring. **What are microglia?** Microglia are the permanent resident immune cells of the CNS. They are located throughout the brain and survey for injury, trauma and disease to initiate a response. They are rarely at rest and constantly monitor synapses. During development, microglia prune excess synapse, which can be linked to developmental disorders such as schizophrenia and ASD. **How does maternal diet alter steroids in the fetus?** A increase of maternal sucrose consumption increases corticosterone in female offspring and the preference of high sugar and high fat diets in male offspring. **What is aldosterone?** Aldosterone is a hormone that manages the salt/water balance and blood pressure. It is secreted by the adrenal glands, situated on top of the kidneys. **Respiratory System** Why do we need to breathe? - General function is to obtain O~2~ for use by the body's cells and to eliminate the CO~2~ the body cells produce - Encompasses two separate but related processes - Internal respiration - External respiration Steps of External Respiration - Ventilation between the atmosphere and air sacs (alveoli) in the lungs - Exchange of O~2~ and CO~2~ between air in the alveoli and the blood in the pulmonary capillaries - Transport of O~2~ and CO~2~ by the blood between the lungs and the tissues - Exchange of O~2~ and CO~2~ between the blood in the systemic capillaries and the tissue cells Anatomy of the Respiratory System - Anatomy consists of - Respiratory airways leading into the lungs - Lungs (airways and alveoli) - Structures of the thorax involved in producing movement of air through the airways into and out of the lungs The Lungs - Found in the thoracic cavity - Two lungs divided into several lobes, each supplied by one of the bronchi - Lung consists of a series of highly branched airways, the alveoli, the pulmonary blood vessels, and large quantities of elastic connective tissue Airways - Tubes that carry between the atmosphere and the air sacs - Nasal passages (nose) - Pharynx (common passageway for respiratory and digestive systems) - Trachea (windpipe) - Fairly rigid, non-muscular tubes - Rings of cartilage preventing collapse - Larynx (voice box) - Right and left bronchi - Bronchioles - No cartilage to hold them open - Walls contain smooth muscle innervated by autonomic nervous system - Sensitive to certain hormones and local chemicals - Alveoli (air sacs) clustered at ends of terminal bronchioles Lung Lobes - Left lung: 2 lobes -- superior and inferior (only has 2 due to heart placement -- cardiac notch) - Right lung: 3 lobes -- superior, middle and inferior Alveoli - Thin-walled, inflatable sacs that function in gas exchange - Walls consist of single layer of flattened Type I alveolar cells - Pulmonary capillaries encircle each alveolus - Type II alveolar cells secrete pulmonary surfactant The Chest Wall - Outer chest wall (thorax) - Formed by 12 pairs of ribs that join sternum anteriorly and thoracic vertebrae posteriorly - Rib cage protects lungs and heart - Chest wall contains muscles involved in generating pressure that causes airflow - External intercostal muscles - Innervated by intercostal nerve - Diaphragm - Dome-shaped sheet of skeletal muscle - Separates thoracic cavity from the abdominal cavity - Innervated by the phrenic nerve - Expiratory muscles - Internal intercostals - Abdominal muscles - Rectus abdominis - Transverse abdominis - External and internal obliques - Onset of expiration begins with relaxation of inspiratory muscles - Relaxation of diaphragm and muscles of the chest wall, plus the elastic recoil of the alveoli, decrease size of the chest cavity - Intrapleural pressure increases, lungs compressed - Intra-alveolar pressure increases - When pressure increases to above atmospheric pressure, air is driven out and expiration occurs The Pleural Space - Pleural sac - Double walled,, closed sac that separates each lung from the thoracic wall - Pleural cavity: interior of pleural sac - Intrapleural fluid - Secreted by surfaces of the pleura - Lubricates pleural surfaces Inspiratory and Expiratory Neurons in the Medullary Centre - Respiratory centres in the brain - Brain stem establish a rhythmic breathing pattern - Medullary respiratory centre - Dorsal respiratory group (DRG) - Mostly inspiratory neurons - Ventral respiratory group (VRG) - Inspiratory neurons - Expiratory neurons pH Regulates Breathing Rate - PaCO~2~ central chemoreceptors (medulla oblongata) - PaO~2~ / Blood pH peripheral chemoreceptors (carotid/aortic arch) - Central and Peripheral Chemoreceptors brainstem respiratory centre muscles of breathing alveolar ventilation **Study Questions** **Explain the anatomy of the respiratory system.** The respiratory system consists of many anatomical structures. They include three main categories; respiratory airways into the lungs, the lungs (including airways and alveoli), and the thorax in producing air movement in and out of the lungs. The lungs are found in the thoracic cavity. They consist of highly branched airways, alveoli, pulmonary blood vessels and elastic connective tissue. The airways include nasal passages, pharynx, trachea (cartilage rings to prevent collapse), larynx, left and right bronchi and bronchioles. Bronchioles do not have cartilage to hold them open. They contain smooth muscle innervated by the autonomic nervous system and are sensitive to hormones and local chemicals. Alveoli are clustered at the end of terminal bronchi. They are thin-walled, inflatable sacs that are used in gas exchange. Type I alveolar cells make up the wall of the alveoli and type II alveolar cells secrete pulmonary surfactant. The outer chest wall is called the thorax. It is formed by 12 pairs of ribs (joined anteriorly at the sternum and posteriorly at the thoracic vertebrae). It protects the lungs and heart and contains muscles that generate pressure for airflow. **What muscles are used for breathing?** There are many muscles involved in the process of breathing. External intercostal muscles are innervated by the intercostal nerve and are instrumental in inhalation. The diaphragm is a dome-shaped sheet of muscle that separates the thoracic cavity from the abdominal cavity. It is innervated by the phrenic nerve and is also important for inhalation. The expiratory muscles include the internal intercostals and the abdominal muscles. The abdominal muscles can be further broken down into Rectus abdominis, Transverse abdominis and external/internal obliques. **Which brain region drives breathing? How is it regulated?** The brain stem is responsible for establishing a rhythmic breathing pattern. The medulla contains the medullary respiratory centre, in which you can find the dorsal and ventral respiratory groups. The DRG consists of mostly inspiratory neurons and the VRG consists of both inspiratory and expiratory neurons. The pons contains the Pontine respiratory group (PRG). Signals are propagated down these neurons to stimulate the contraction of the muscles for inhalation and exhalation. **Can slower breathing reduce stress? Explain an experiment.** Slower breathing can reduce stress. An experiment to test this was done on rats in an operant chamber with varying strobe light conditions; sometimes relating to respiration rate and sometimes not (the yoked control). It was observed that the animals that were conditioned to slow their breathing rate in response to a stressor had an overall lower respiration rate in further stress tests. **Urinary System** Kidney Function - Regulating the body's water level, molecule concentrations in the blood, pH - Influence red blood cell production and blood pressure - Filtering blood for nitrogenous compounds from protein degradation - Main route for eliminating potentially toxic metabolic wastes and foreign compounds from the body - Bring back useful compounds into the blood - Liver can direct dead cell and toxic waste to bowels or urinary system - Lungs get rid of CO~2~ How Do We Get Energy? - Metabolizing proteins/amino acids from food - Taken up into blood from digestive system - Amino acids have amine group - Energy stored as carbs or fats - Ammonia is created - NH~3~ is metabolized into urea and filtered by the kidneys into urine and excreted How Big Are Your Kidneys? - About fist sized - Adrenal gland sits on top Where Are The Kidneys Located? - Posterior to the peritoneal cavity (lower back) - Aorta brings blood, inferior vena cava removes blood - Kidneys hold about 20% of total blood volume How Are The Kidneys Filtering Blood? - The nephron - Functional unit of the kidney - Smallest unit that can perform all the functions of the kidneys - Approximately 1 million nephrons per kidney - Juxtamedullary nephron - Long-looped nephron important in establishing the medullary vertical osmotic gradient - Cortical Nephron - Most abundant type of nephron Cortical and Juxtamedullary Nephrons - All nephrons originate in the cortex - Glomeruli of cortical nephrons lie in the outer layer of the cortex - About 80% of nephrons - Glomeruli of juxtamedullary nephrons lie in the inner layer of the cortex - Perform most of the urine concentration Steps of Filtration - Glomerular filtration - Non-discriminant filtration of a protein-free plasma from the glomerulus into Bowman's capsule - Tubular reabsorption - Selective movement of filtered substances from the tubular lumen into the peritubular capillaries - Tubular secretion - Selective movement of nonfiltered substances from the peritubular capillaries into the tubular lumen Overview of Functions of Parts of a Nephron - Vascular component - Afferent arteriole -- carries blood to the glomerulus - Glomerulus -- a tuft of capillaries that filters a protein-free plasma into the tubular component - Efferent arteriole -- carries blood from the glomerulus - Peritubular capillaries -- supply the renal tissue; involved in exchanges with fluid in the tubular lumen - Tubular Component - Bowman's capsule -- collects the glomerular filtrate - Proximal tubule -- uncontrolled reabsorption and secretion of selected substances occur here (ions, glucose, water) - Cells with microvilli - Loop of Henle -- creating concentration gradient to pump out water back into blood - Distal tubule -- variable, controlled reabsorption of Na+ and H~2~O and secretion of K+ and H+ occur here; fluid leaving the collecting duct is urine, which enters the renal pelvis - Some urea is recycled, further concentration of urine Pressure Changes within the Urinary Bladder as the Bladder Fills with Urine - Increased pressure leads to an increased signal to expel urine How do Hormones Affect Kidney Function? - Aldosterone - Secreted by adrenals - Causes kidneys to increase salt and water reabsorption into the bloodstream to increase blood volume - Restores salt levels and blood pressure - ADH -- antidiuretic hormone (vasopressin) - Secreted by posterior pituitary - Helps the body to retain water and stay hydrated (DCT) - ADH increased water reuptake in collecting duct, concentrates urine - Caffeine and alcohol make you have to pee a lot - Inhibit ADH, inhibiting water reuptake and dehydrating the body **Study Questions** **Identify the functional anatomy involved in urine production and excretion.** The kidneys are the main organ involved in urine production. Additionally, the bladder, urethra and ureter are key players in urine excretion. **Identify the distinct regions of the nephron.** All nephrons originate in the cortex. The glomerulus is a tuft of capillaries that filters a protein free plasma into the tubular component. Peritubular capillaries supply the renal tissue and are involved in exchanging fluid in the tubular lumen. The Bowman's capsule collects glomerular filtrate. The proximal convoluted tubule are cells with microvilli that reabsorb ions, glucose and water. The Loop of Henle creates a concentration gradient to pump the water back into the blood. The distal convoluted tubule recycles some urea and further concentrates the urine. **Differentiate between cortical and juxtamedullary nephrons.** A cortical nephron is more abundant than a juxtamedullary nephron. Its glomerulus sits in the outer layer of the cortex and accounts for about 80% of nephrons. Juxtamedullary nephrons have a longer Loop of Henle. Their glomerulus is located in the inner layer of the cortex. They perform more urine concentration activities and account for about 20% of nephrons in the kidney. **zDistinguish between filtration, reabsorption, secretion and excretion.** Glomerular filtration is non-discriminant and occurs at the glomerulus of a nephron. It filters a protein free plasma into the Bowman's capsule. The filtered substance then undergoes reabsorption; the selective movement of filtered substances from the tubular lumen into the peritubular capillaries. Finally, it undergoes tubular secretion in which selective movement on non-filtered substances from the peritubular capillaries are moved into the tubular lumen. **Describe the effects of vasopressin and aldosterone.** Aldosterone causes the kidneys to increase their salt and water reabsorption into the bloodstream to increase blood volume in order to restore these levels. Vasopressin, also known as ADH helps the body retain water, staying hydrated. The increases water uptake occurs in the collecting duct and concentrates the urine. **Describe the reflex and voluntary control of micturition.** Micturition is the fancy word for urination. This process is governed by reflex and voluntary control. The micturition reflex is initiated when the stretch receptors in the bladder wall are stimulated. Increased distention increases the receptor activation. Afferent fibres carry impulses to the spinal cord and stimulate the parasympathetic supply to the bladder, inhibiting the motor neuron supply to the external sphincter. This parasympathetic stimulation causes the bladder to contract. The external sphincter relaxes as its motor neuron supply is inhibited, making both sphincters open and expelling urine. This is the process that occurs in infants. In voluntary control, the same process occurs, however, bladder fullness appears before the relaxation of the external sphincter. This is a learned habit and taught through potty training young children. The external sphincter cannot remain closed forever, and therefore the warning signs should always be taken into consideration. Urination can also be deliberately initiated by relaxing the external sphincter and the pelvic diaphragm. **Extra Review of Difficult Concepts** Muscle Function - Controlled muscle contraction allows purposeful movement of the whole body or parts of the body - Manipulation of external objects - Propulsion of contents through various hollow internal organs - Emptying of contents of certain organs to external environment Structure of Skeletal Muscle - Muscle consists of a number of muscle fibres lying parallel to one another and held together by connective tissue - A single skeletal muscle cell is known as a muscle fibre - Multinucleated - Large, elongated and cylindrically shaped - Fibres usually extend entire length of muscle Myosin - Component of thick filament - Protein molecule consisting of two identical subunits shaped somewhat like a golf club - Tail ends intertwined around each other - Globular heads project from one end - Heads form cross bridges between thick and thin filaments - Cross bridge has two important sites critical to contractile process - Actin-binding site - Myosin ATPase (ATP-splitting) site Actin - Primary structural component of thin filaments - Each actin molecule has special binding site for attachment with myosin cross bridge - Binding results in contraction of muscle fibre - Actin and myosin are often called contractile proteins - Neither one actually contracts - Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells Tropomyosin and Troponin - Tropomyosin: Thread-like molecules that lie end-to-end alongside the groove of the actin spiral - In this position, they cover actin binding sites, blocking the interaction that leads to muscle contraction - Troponin is made of three polypeptide subunits: - One binds to tropomyosin - One binds to actin - One can bind with Ca^2+^ - When not bound to Ca^2+^, troponin stabilizes tropomyosin in blocking the position over actin's cross bridge binding sites - When Ca^2+^ binds to troponin, tropomyosin moves away from the blocking position - With tropomyosin out of the way, actin and myosin bind and interact at cross bridges Linkage of Motor Neurons and Skeletal Muscle Fibres - An action potential in a motor neuron propagates to skeletal muscle along efferent fibres - Axon terminals form a neuromuscular junction with muscle fibres - Axon terminal - Terminal button - Motor end plate - Axon terminal of motor neurons forms neuromuscular junction with a single muscle cell - Signals are passed between nerve terminal and muscle fibre by meanas of neurotransmitter ACh - Released ACh binds to receptor sites on motor end plate of muscle cell membrane Acetylcholine - Neurotransmitter - Carries action potential across synapse to muscle fibre Formation of an End Plate Potential - Binding triggers the opening of specific channels in motor end plate - Ion movements depolarize motor end plate, producing end plate potential - Local current flow between depolarized end plate and adjacent muscle cell membrane brings adjacent areas to threshold - Action potential is initiated and propagated throughout the muscle fibre Acetylcholinesterase and Acetylcholine Activity - Acetylcholinesterase (AChE) inactivates ACh - Ends the end plate potential and the action potential and the resultant contraction - Removes most ACh within a few milliseconds after release Excitation-Contraction Coupling - Series of events linking muscle excitation to muscle contraction - Muscles stimulated to contract with release of ACh - ACh is a neurotransmitter, a chemical that carries messages from your brain to your body trough nerve cells -- excitatory neurotransmitter - ACh operates as a neurotransmitter in many parts of the body, but it is most commonly associated with the neuromuscular junction Spread of Action Potential down the T Tubules - At A band and I band, surface membrane dips to form a transverse tubule (T tubule) - Runs perpendicular from the surface into the central portion of the muscle - Action potentials spread down T Tubules Release of Calcium from the Sarcoplasmic Reticulum - Modified ER - Consists of fine network of interconnected compartments that surround each myofibril - Not continuous but encircles myofibril throughout its length - Segments are wrapped around each A band and each I band Relaxation - Depends on the reuptake of Ca^2+^ into SR - AChE breaks down ACh at neuromuscular junction - Muscle fibre action potential stops - When local action potential is no longer present, Ca^2+^ moves back into SR Contractile Activity - Latent period: time delay between stimulation and the onset of contraction - Contraction time: time from onset of contraction until peak tension develops - Time varies depending on muscle fibre type Pulmonary Vs. Systemic Circulation - Pulmonary circulation - Closed loop of vessels carrying blood between heart and lungs - Systemic circulation - Circuit of vessels carrying blood between heart and other body systems - Heart positioned between two bony structures: sternum and vertebrae Comparison of Right and Left Pumps - Both sides of the heart simultaneously pump equal amounts of blood - Pulmonary circuit is low-pressure, low-resistance - Systemic circuit is high-pressure, high-resistance - When pressure is greater behind the valve, it opens - When pressure is greater in front of the valve it close, it will not open in the opposite direction The Heart Walls - Three distinct layers - Endothelium (endocardium) - Thin inner tissue - Epithelial tissue that lines entire circulatory system - Myocardium - Middle layer - Composed of cardiac muscle - Constitutes bulk of heart wall - Epicardium - Thin external layer that covers the heart The Pericardial Sac - Heart is enclosed by pericardial sac - Pericardial sac has two layers - Tough fibrous covering - Secretory lining - Secretes pericardial fluid - Provides lubrication to prevent friction between pericardial layers - Pericarditis - Inflammation of pericardial sac - Myocarditis - Inflammation of heart muscle Electrical Activity of the Heart - Heartbeats rhythmically as result of action potentials it generates by itself (autorhythmicity) - Twp specialized types of cardiac muscle cells - Contractile cells - 99% of cardiac muscle cells - Do mechanical work of pumping - Normally do not initiate own action potentials - Autorhythmic cells - Do not contract - Specialized for initiating and conducting action potentials responsible for contraction of working cells The Sinoatrial Node - Locations of non-contractile cells capable of autorhythmicity - Sinoatrial Node (SA Node) - Specialied region in right atrial wall near opening of superior vena cava - Pacemaker of the heart - Atrioventricular node (AV node) - Small bundle of specialized cardiac cells located at the base of right atrium, near septum - Bundle of His (atrioventricular bundle) - Cells originate at AV node and enter the interventricular septum - Divides to form the right and left bundle branches, which travel down the septum, curve around tip of ventricular chambers, travel back toward atria along outer walls