HUBS1404 Biomedical Science 2 Notes PDF

Biomedical Science 2 – HUBS1404 – amistry Contents Lecture 1: Overview of the Cardiovascular System......................................................................... 10 Heart Section and Basic Structure................................................................................................ 10 The Need for the Circulatory System........................................................................................... 10 Circulatory System Structure and Description.............................................................................. 11 Lecture 2: Anatomy of the Heart...................................................................................................... 12 Function of the Heart Valve.......................................................................................................... 13 Fibrous Tissues of the Heart......................................................................................................... 14 Coronary Arteries and Veins......................................................................................................... 14 Lecture 3: Cardiac Conduction System............................................................................................ 15 Structure of Cardiac Muscle Fibre and Intercalated Disks........................................................... 15 Autorhythmic Action Potentials.................................................................................................... 15 Cardiac Contractile Fibres............................................................................................................ 16 ECG Trace and Diagnostics.......................................................................................................... 17 Modulatory Effects by ANS......................................................................................................... 18 Lecture 4: Blood Vessels and Haemodynamics................................................................................ 19 Blood Vessel Structure.................................................................................................................. 19 Arteries and Veins Differences..................................................................................................... 19 Capillary Types............................................................................................................................. 20 Blood Flow and Blood Pressure.................................................................................................... 21 Major vasodilators and constrictors.............................................................................................. 22 Lecture 5: Tissue Perfusion and Fluid Recovery.............................................................................. 23 Capillary Exchange....................................................................................................................... 23 Transport Modes........................................................................................................................... 23 Filtration and Absorption.............................................................................................................. 24 Reperfusion/ Reoxygenation Injury.............................................................................................. 25 Lecture 6: Blood Volume and Pressure Regulation.......................................................................... 26 Regulation of Blood Volume and Pressure................................................................................... 26 Modulating Stroke Volume........................................................................................................... 28 Hypertension (High BP)................................................................................................................ 29 Lecture 7: The Respiratory System................................................................................................... 30 Organisation of the Respiratory System....................................................................................... 30 Major Components........................................................................................................................ 30 Structure of Airways and Alveoli................................................................................................. 32 Gas Exchange Efficiency.............................................................................................................. 33 Lecture 8: Pulmonary Respiration.................................................................................................... 34 Air Pressures and Pulmonary Ventilation..................................................................................... 34 Respiratory Muscles for Pulmonary Ventilation........................................................................... 34 Lung Volumes and Capacities...................................................................................................... 35 CNS and PNS in Breathing Regulation........................................................................................ 36 Lecture 9: Gas Exchange.................................................................................................................. 38 Partial Pressure of Gas.................................................................................................................. 38 Gas Solubility in the Respiration System..................................................................................... 38 O2 and CO2 Transport................................................................................................................... 39 Lecture 10: Ventilation, Perfusion and Airflow Control.................................................................. 42 Ventilation/ Perfusion Ratio.......................................................................................................... 42 Physiological Response to Ventilation/ Perfusion........................................................................ 42 Pulmonary Disorders.................................................................................................................... 43 Bronchoconstriction and Dilation................................................................................................. 44 Lecture 11: Respiration inBalance and System Integration.............................................................. 45 Acidosis Effect on the Body......................................................................................................... 45 Alkalosis Effect on the Body........................................................................................................ 45 Blood pH Maintenance................................................................................................................. 45 Respiratory System and Cardiovascular System Cooperation...................................................... 46 Ageing and the Respiratory System.............................................................................................. 46 Lecture 12: Energy Metabolism I..................................................................................................... 47 Metabolism................................................................................................................................... 47 Structure of ATP........................................................................................................................... 47 Oxidation and Reduction.............................................................................................................. 47 Glucose Catabolism...................................................................................................................... 48 Lecture 13: Energy Metabolism II.................................................................................................... 51 Mechanisms of Glucose Anabolism............................................................................................. 51 Lipid Metabolism and Lipolysis................................................................................................... 51 Fatty Acids.................................................................................................................................... 52 Lipoproteins.................................................................................................................................. 53 Protein Metabolism....................................................................................................................... 54 Lecture 14: Digestive System I......................................................................................................... 55 The 6 Main Functions................................................................................................................... 55 Layers of the Gastrointestinal Tract.............................................................................................. 55 Major Digestive System Components........................................................................................... 56 Histology of the Stomach, Small Intestine and Large Intestine.................................................... 57 Lecture 15: Digestive System II........................................................................................................ 59 Saliva Composition....................................................................................................................... 59 Gastric Gland Cells....................................................................................................................... 59 Liver and Pancreas in Digestive System....................................................................................... 60 Digestion and Absorption............................................................................................................. 61 Role of Endocrine and Nervous Systems...................................................................................... 62 Lecture 16: Pancreas, Liver and Metabolism.................................................................................... 63 Pancreas Features and Structure................................................................................................... 63 Composition and Function of Pancreatic Juice............................................................................. 63 Hepatocyte Structure..................................................................................................................... 64 Bile Pathway and Composition..................................................................................................... 65 Liver Function............................................................................................................................... 65 Lecture 17: Metabolic Adaptations................................................................................................... 67 Absorptive and Postabsorptive States........................................................................................... 67 Effects of Fasting and Starvation.................................................................................................. 69 Effects of Imbalanced Energy Intake/ Expenditure...................................................................... 69 Lecture 18: Renal System I............................................................................................................... 71 Kidney Anatomy........................................................................................................................... 71 Nephron Structure......................................................................................................................... 71 Blood Supply................................................................................................................................ 72 Renal Corpus................................................................................................................................. 72 Renal Corpus Tubules................................................................................................................... 72 Ureters, Urinary Bladder and Urethra Structure........................................................................... 73 Lecture 19: Renal System II............................................................................................................. 75 Net Glomerular Filtration.............................................................................................................. 75 Glomerular Filtration Rate............................................................................................................ 76 GFR Autoregulation...................................................................................................................... 76 Glomerular Disease....................................................................................................................... 77 Lecture 20: Renal System III............................................................................................................ 78 Tubular Reabsorption and Secretion............................................................................................. 78 PT, Nephron Loop and DT Difference in Reabsorption/ Secretion.............................................. 78 Reabsorption Rate......................................................................................................................... 79 Lecture 21: Fluid and Electrolyte Balance........................................................................................ 81 Fluid Distribution and Major Solutes............................................................................................ 81 Pathways of Water Gain and Loss................................................................................................ 81 Water Loss Regulation.................................................................................................................. 82 Counter Current Multiplication..................................................................................................... 83 Overhydration............................................................................................................................... 83 Lecture 22: Mineral Balance............................................................................................................. 84 Calcium......................................................................................................................................... 84 Phosphate...................................................................................................................................... 84 Sulphur.......................................................................................................................................... 86 Magnesium.................................................................................................................................... 86 Iron................................................................................................................................................ 86 Lecture 23: Acid-Base Balance......................................................................................................... 87 Buffering Systems for pH............................................................................................................. 87 Acidity and Acidosis..................................................................................................................... 87 Protein Buffering Systems............................................................................................................ 87 Phosphate Buffering Systems....................................................................................................... 88 Renal System in Acid-Base Balance............................................................................................. 88 Lecture 24: Anthropogeny................................................................................................................ 89 What is Anthropogeny?................................................................................................................ 89 Darwin’s Theory of Evolution...................................................................................................... 89 Natural selection........................................................................................................................... 89 Causes of Genetic Variation......................................................................................................... 90 Key Events in Human Evolution.................................................................................................. 91 Lecture 25: Introduction to Reproductive System............................................................................ 92 Sexual Reproduction..................................................................................................................... 92 Structure and Function of Reproductive Organs........................................................................... 92 Cell Division................................................................................................................................. 95 Lecture 26: Hormonal Control of Reproduction............................................................................... 96 Endocrine Function....................................................................................................................... 96 Regulation of the Reproductive Function..................................................................................... 96 The Ovarian Cycle Phases............................................................................................................ 97 The Uterine Cycle Phases............................................................................................................. 98 Lecture 27: Human Development..................................................................................................... 99 Oogenesis to Fertilisation.............................................................................................................. 99 Human Devleopment and Organogenesis................................................................................... 102 Lecture 28: Introduction to the Immune System............................................................................. 104 The Lymphatic System............................................................................................................... 104 Immune System Divisions.......................................................................................................... 104 Lecture 29: Innate Immunity.......................................................................................................... 109 Antimicrobial Proteins................................................................................................................ 111 Lecture 30: Acquired Immunity...................................................................................................... 113 Adaptive Immunity..................................................................................................................... 113 Antigens – Clonal Selection Theory........................................................................................... 113 Antibodies................................................................................................................................... 116 Lecture 1: Cardiovascular System Overview - Name the key elements of the cardiovascular system - Define the three sections of the heart wall - Explain why multicellular organisms require a circulatory system - Describe the two circuits that make up the human circulatory system Lecture 2: Heart Anatomy - Define the four heart chambers and four heart valves - Describe the blood vessels leading into and out of the heart chambers - Explain the function of the heart valves during a normal heart beat/cycle - Identify the flow of blood through the heart from the vena cavae to the aorta - Describe the blood flow in the coronary arteries and veins Lecture 3: Cardiac Conduction System - Describe the structure of cardiac muscle fibres - Explain the structure and function of intercalated disks - Discuss the series of events in the heart’s intrinsic conduction pathway - Define the action potentials of both autorhythmic and contractile heart fibres - Explain the key events in an ECG - Describe how our nervous system modulates heart rate Lecture 4: Blood Vessels and Haemodynamics - Define the three main types of blood vessels and list their different structures and features - Explain the effects of pressure difference and vascular resistance on blood flow - Define mean arterial pressure and chart its change from aorta to large veins - State the three main factors affecting vascular resistance - Describe the major vasodilators and vasoconstrictors and how they exert their affects Lecture 5: Tissue Perfusion and Fluid Recovery - Define the three types of capillaries and list their different structures and features - Explain the three capillary exchange mechanisms - Describe the process of capillary filtration and reabsorption via hydrostatic and osmotic pressures - Discuss venous return and the factors that facilitate this process - Explain the key factors involved in reperfusion injury Lecture 6: Blood Volume and Pressure Regulation - Describe the mechanisms of both neural and endocrine regulation of blood pressure, including receptors and effector pathways - Define end-diastolic volume, end-systolic volume, stroke volume and ejection fraction in relation to heart function - Explain preload, contractility and afterload in relation to heart function - Define a positive and negative inotropic agent - Discuss the key factors responsible for hypertension and explain ways to reduce it Lecture 7: Organisation of the Respiratory System - List the major components of the upper and lower respiratory tracts - Discuss the passage of air from outside the body to the alveoli - Describe the changes in structure that occur in the different bronchial tubes - Explain the changes in epithelial tissue from the trachea to the alveoli - Describe the structure of the alveoli and respiratory membrane Lecture 8: Pulmonary Respiration - Describe the process of pulmonary ventilation by applying Boyle’s law - Explain the differences in atmospheric, alveolar and intrapleural pressures during pulmonary ventilation - List the main muscles responsible for pulmonary ventilation - Discuss the roles of surface tension, compliance and airway resistance - Identify the different lung volumes and capacities - Describe the key factors responsible for regulation of breathing Lecture 9: Gas Exchange - Define partial pressures and be able to calculate the partial pressure of a single gas - Describe gas solubility in a liquid in relation to gas partial pressure and solubility - Explain the role partial pressures and solubility play in the movement of oxygen and carbon dioxide from the atmosphere to the cells - Describe oxyhaemoglobin saturation and the key factors that affect this Lecture 10: Ventilation, Perfusion and Airflow Control - Discuss the differences in both alveolar ventilation and pulmonary capillary perfusion rates in the lungs - Explain the mechanisms employed to match ventilation and perfusion rates - List the three different types of lung disease - Describe the key features of common restrictive and obstructive pulmonary diseases/disorders - Explain how the nervous and endocrine systems can modulate lung airway diameter Lecture 11: Respiration in PH Balance and System Integration - Define the normal blood pH range - Describe the key causes and mechanisms of: o Respiratory acidosis and alkalosis o Metabolic acidosis and alkalosis - Explain the role of the respiratory system in maintaining homeostatic pH range - Describe the combined effects of the respiratory and CV systems to exercise - List the key effects of ageing on the respiratory system Lecture 12: Energy Metabolism I - Define anabolic and catabolic metabolism - Describe the key factors involved in both oxidation and reduction reactions - Define endergonic and exergonic reactions - Explain the key reactions and products of glucose catabolism during: o Glycolysis o The Krebs cycle o Oxidative phosphorylation Lecture 13: Energy Metabolism II - Describe the mechanisms of glycogenesis and gluconeogenesis - Explain why we store most of our excess energy in the form of triglycerides - List the events that occur in the catabolism of lipids for beta oxidation - Discuss the processes involved in transporting lipids - Describe the products of protein catabolism - Explain the processes involved in protein deamination and transamination Lecture 14: Digestive System I - List the key elements of the digestive system - Describe the six functions - Define the four layers of the G I tract and list their key properties - Explain the structure and histology of the stomach, small intestine and large intestine Lecture 15: Digestive System II - List the various secretions into the GI tract’ - Describe the structure of gastric glands and list their specific cells and secretions - Discuss the role of bile and pancreatic juice in digestion and absorption - Explain the absorption pathways of carbohydrates, proteins and lipids - Discuss the role of the endocrine and nervous systems on digestion and absorption Lecture 16: Pancreas, Liver and Metabolism - List the cells responsible for the pancreas’ endocrine and exocrine functions and define their mechanisms of action - Describe the pancreatic ducts and their association with the bile duct - Explain the main functions of the liver - Describe the blood and bile flow to and from hepatocytes - Discuss the role of bile as an excretory product and in lipid digestion Lecture 17: Metabolic Adaptations - Define absorptive and postabsorptive states - Explain the pathways of glucose, lipids and proteins in the absorptive state - Describe the mechanisms for maintaining ATP production in the postabsorptive state - List the hormones used during both the absorptive and postabsorptive states and their key actions - Discuss ketone bodies and explain their production and use Lecture 18: Renal System I - Define the key functions of the kidneys - Describe the gross structure of the kidney, including the cortex, medulla and pyramids - Explain the structure of the renal nephron - Discuss the blood flow from the renal artery to the renal vein - Describe the key functions of the glomerular capsule and renal tubule - Identify the ureters, bladder and urethra Lecture 19: Renal System II - Discuss the importance of glomerular filtration - Explain the three factors affecting net glomerular filtration - Define the mechanisms of renal autoregulation, neural regulation and hormonal regulation of GFR - Describe the effects of a glomerular inflammation on an individual Lecture 20: Renal System III - Describe the blood vessels involved in reabsorption and secretion - Explain the structural and functional differences between the proximal tubule, nephron loop, distal tubule and collecting duct - List the key substances reabsorbed at each specific region of the renal tubule Lecture 21: Fluid and Electrolyte Balance - Describe the distribution of water in the human body - List the key actions responsible for water gain and loss - Explain the key neural and hormonal mechanisms used to maintaining water balance - Discuss the differences in osmolality in different areas of the kidney and renal tubule - Describe the differences between urine formation in a hydrated and dehydrated state Lecture 22: Mineral Balance - Describe the functions of calcium, phosphate, sulphur, magnesium and iron in the body - Explain their regulatory mechanisms Lecture 23: Acid-Base Balance - Buffering systems help maintain the pH of body fluid - Increases in acidity can cause denaturing of proteins and loss of function - Protein and phosphate buffering systems operate to either increase or decrease pH as required - Kidneys can secrete hydrogen ions using differing mechanisms to maintain blood pH Lecture 24: Anthropogeny - Define anthropogeny and evolution by natural selection - Describe the three main factors involved in genetic variability - Discuss anatomical and genetic homologies - Explain the major events in human evolution Lecture 25: Introduction to Reproductive System - Discuss the advantages and disadvantages of sexual reproduction - Describe the key organs and accessory structures of the male and female reproductive systems - Explain the stages of both spermatogenesis and oogenesis - Compare mitosis and meiosis - Describe the stages of meiosis and the transition from diploid to haploid cells Lecture 26: Hormonal Control of Reproduction - Define the two major gonadotropins and explain the control of these via the hypothalamic- pituitary axis - Describe the main effects of follicle stimulating hormone and luteinising hormone in both male and female reproductive systems - Discuss the events of both the ovarian and uterine cycles - Describe the roles played by oestrogen, progesterone and testosterone in the male and female reproductive systems Lecture 27: Human Development - Explain the process involve in fertilisation - Discuss the preimplantation developmental steps - Describe the key events occurring during implantation - Explain the process of gastrulation - List the key events of placentation - Discuss organogenesis and the development of the foetus - Explain the major physiological adjustments that occur in the infant at, and in the firsts weeks after birth Lecture 28: Introduction to the Immune System - Describe the basic components of our immune system - Discuss the lymphatic system - Define the different types of white blood cells and their functions - Explain the function of lymph nodes, the spleen and MALT Lecture 29: Innate Immunity - Define the major components of the Innate Immune System - Describe the process of inflammation - Discuss the role of complement proteins and interferon - Explain the causes and role of fever Lecture 30: Acquired Immunity - Define the key aspects of the adaptive immune system - Describe an antigen - Understand the roles of B cells and T cells - Explain the structure and function of antibodies Lecture 1: Overview of the Cardiovascular System Heart Section and Basic Structure Components of CVS The CV system is made of the heart, blood and blood vessels. The heart pumps the blood, arteries away from heart and veins back to heart. The capillaries permit nutrients, waste and gas exchange. Position, Layers and Size of Heart The heart sits near the anterior (front) of the chest, behind the sternum and sits in the middle section of chest, slightly to left. The heart is surrounded by the lungs. There are 4 chambers and contains a double pump. The heart wall contains 3 layers: the epicardium/visceral pericardium (the outer layer), the myocardium (muscular wall of heart, cardiac muscle tissue/ vasculature and nerves) and endocardium (inner layer, epithelium cell lining). The pericardium has two main parts: the fibrous pericardium (touch, dense, irregular connective tissue, provides protection and anchors the heart) and the serous pericardium (thinner, delicate membrane, double layer, produces pericardial fluid for lubrication). The inner visceral and outer parietal layer of the serous pericardium are separated by a cavity filled with serous fluid. Heart is about the size of a fist and is not reliant on nervous system for activation. Pumps 14,000 L of blood a day. The Need for the Circulatory System Cells require oxygen and nutrients from the environment and produce CO2 and waste that needs to be removed. Multicellular organisms cannot rely on simple diffusion and its concentration gradients, rather they rely on circulatory systems. The external cell is able to get nutrients first, internal last, hence, to maintain homeostasis nutrients and oxygen must be passed around via circulatory systems. Circulatory System Structure and Description There are 2 major complex human vascular circuits that both occur at the same time. Pulmonary Circuit The pulmonary circuit is used to oxygenate the blood and remove carbon dioxide. Systemic Circuit The systemic circuit supplies the cells with oxygen and nutrients and remove waste and carbon dioxide. Lecture 2: Anatomy of the Heart Heart Chamber Structure Functions Right Atrium Has auricles (flaps of cells) over its Receives blood from veins (blood surface which allows for the heart vessels returning deoxygenated expansion. blood to the heart). Its main vessels Has pectinate muscles on the are the inferior vena cava (body) and anterior walls and inner auricle superior vena cava (brain) and surface which are prominent coronary veins. muscular ridges. Myocardium thickness: 2-3 mm Right Ventricle Has a thicker myocardium (4- Ejects blood from the heart into 5mm). Interior surface contains blood vessels called arteries. ridges called vebeculae carneae. Cone muscles called papillary muscles extend from ventricle base. Left Atrium Has few pectinate muscles on Receives blood from veins (blood anterior inner surface (near the vessels returning deoxygenated auricles) blood to the heart). Left Ventricle The thickest heart chamber (10-15 Ejects blood from the heart into mm). The myocardium is required blood vessels called arteries. to generate enough pressure to force the blood through the systemic circuit. The inner surface contains trabecula corneae. Also has papillary muscles. - The left and right atria are divided by the interatrial septum. - The ventricles have little differences, main difference is the pressure. Pectinate Muscles: parallel muscular ridges in the walls of atria Trabeculae Carneae: Rounded/ irregular muscular columns projecting from inner surface of ventricles Chordae Tendinea: Strong, fibrous connections between the valve leaflets and the papillary muscles. Papillary muscles: Pillar like muscles in ventricle cavities. The heart has its own skeleton which are dense connective tissue rings around each of the 4 valves which helps prevent the valves from stretching under load. It acts as an insertion point for cardiac muscle cells and electrically insulates the atria from the ventricles. Function of the Heart Valve The blood must follow a specific path within the heart through certain chambers and this process is supported by heart valves. The human heart has 4 valves: 2 atrioventricular valves and 2 semilunar valves. These valves help prevent backflow. The Atrioventricular Valves They are located between the atria and the ventricles. Their key components are cusps that hold open and close and a chordae tendinea (tendinous cords) that prevent the cusps from eversion. The right AV valve has three cusps known as the tricuspid valve. The left AV valve has two cusps known as the bicuspid or mitral valve. When these valves are open, the ventricles fill with blood as the cusps project downwards. Then the ventricle contraction occurs, and the blood pressure forces the cusps closed. This directs blood up through the semilunar valves. The papillary muscles contract to hold cords taut. The Semilunar Valves They are simple valves with cusps having a half-moon shape. There are 2 semilunar valves, one aortic value at base of aorta and a pulmonary valve at base of pulmonary trunk. The semilunar valve open when blood pressure in the two ventricles is higher than the aorta and pulmonary trunk. The high pressure forces the cusps apart and allows blood flow. The pair of AV valve and semilunar valve work simultaneously, one is open and the other closed. The pressure of the blood can force the aortic valve open and mitral valve shut during contraction. Whilst the muscle is relaxed, the mitral valve is naturally open, and the blood fills the ventricles. Fibrous Tissues of the Heart Cardiac cells require high amounts of nutrients and oxygen; hence the heart has its own blood supply. Coronary arteries feed working cardiac tissue and emerge at the base of the aorta. The coronary veins return this blood by merging into the coronary sinus. Coronary Arteries and Veins The right and left coronary arteries feed from base of ascending aorta. The veins from heart tissue drains to the coronary sinus by the cardiac veins. The coronary sinus empties blood into the right atrium near base of vena cava. Lecture 3: Cardiac Conduction System The heart muscle is unique as it does not rely on the system for activation. Both skeletal and smooth muscle does rely on the nervous system. The heart muscle instead relies on autorhythmic fibres and special cell junctions. The heart muscle is activated in sequence, not at the same time. Structure of Cardiac Muscle Fibre and Intercalated Disks Heart muscle fibres share similarities with skeletal muscle as they also have the striations and the sarcomeres. But the fibres are much shorter, less circular and have larger mitochondria. They have multiple branches connecting to neighbouring fibres. Fibres are connected through intercalated disks, which are irregular thickenings of the sarcolemma. They contain desmosomes which attach the sarcolemma together and contain gap junctions which permit ion passage and facilitate AP conduction. There are2 types of cardiac cells: pacemaker and contractile. Autorhythmic Action Potentials The heart’s electrical activity and muscle contraction is due to the action of autorhythmic fibres. These specialised fibred spontaneously generate APs that spread by gap junctions, even outside the body. These autorhythmic fibres act as natural pacemakers and set the rhythm of the heart. They collectively form the heart’s conduction system by activating the heart’s contractile muscle fibres. This ensures each section of myocardium contracts at the appropriate time which is essential for the double pump ability. The electrical activity begins in the sinoatrial (SA) node, the autorhythmic fibres depolarise and repolarise (due to no stable resting potential) and spread the APs across the left atria through gap junctions. Both atria myocardium contract at the same time. The atrioventricular (AV) node then slows the AP due to the bottle neck cell structure (100m/s), this delay allows the ventricles to fill with blood. The AV bundle (bundle of His) is vital for conduction of action potential from atria to the ventricles. The atrioventricular branches (left and right) run down the interventricular septum to apex of heart. Then the Purkinje fibres runs from the bundle branches up the ventricle walls and has large diameter fibres, this rapidly speed up the AP and results in ventricular contraction. The autorhythmic cell action potential slowly depolarises compared to neurons as calcium is the cause of depolarisation. Repolarization occurs when potassium gates open and calcium channels shut. Rates of depolarization vary in the heart’s conduction pathway: SA Node: 100x a minute. AV Node: 40-60x a minute. AV bundle, bundle branches and Purkinje fibres: 20-35x a minute. Cardiac Contractile Fibres Contractile fibres have a stable resting membrane potential around -90mV. The depolarisation is initiated by neighbouring cells through gap junctions. They cause rapid opening of voltage gated sodium channels and sodium influx down the electrochemical gradient, causing depolarisation. The plateau phase is a period of maintained depolarisation (0.25 seconds) caused by voltage gated sodium channels in the sarcolemma. The increase in calcium in cytosol triggers contraction. The repolarisation is caused by potassium gates opening to return the resting membrane potential of -90mV. ECG Trace and Diagnostics An electrocardiogram (ECG) is a device that measures the electrical activity of the heart which is caused by muscle contraction. Usually, a 12 lead ECG is used which has 10 electrodes attached to various parts of the chest and limbs. This allows the electrical activity to be viewed from multiple angles. There are many components to the ECG. The P wave is the SA node through contractile fibres. The QRS complex is the electrical activity in the ventricles involving depolarisation. The T wave is repolarization of the ventricles. The PQ interval is the conduction time from the atria to the start of the ventricles (AV Node to AV bundle). The ST segment is the time og ventricular contractile fibre depolarising. The QT interval represents the time from the beginning of ventricular depolarisation to repolarization. Generally, interval is a wave whilst segment is maintained. The cardiac output (CO) is the volume of blood pumped per minute. Stroke volume is the volume of blood pumped by the left ventricle per minute (about 70ml). On average, resting heart rate is 75 bpm. 𝐶𝑂 = 𝑠𝑡𝑟𝑜𝑘𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 𝑥 ℎ𝑒𝑎𝑟𝑡 𝑟𝑎𝑡𝑒 Average cardiac output is 5.25 L. Modulatory Effects by ANS Parasympathetic activity via the vagus nerve releases acetylcholine (Ach). This decreases depolarisation rate in SA and AV nodes and hence decreases heart rate. Sympathetic activity via the cardiac accelerator nerves released norepinephrine (noradrenaline). This increases depolarisation rate in SA and AV nodes and hence increases heart rate. The natural SA node depolarisation rate is 100x a minute. Lecture 4: Blood Vessels and Haemodynamics Blood Vessel Structure Blood is vital for life, it circulates around the body through arteries, which carry blood away from the heart. The arteries reduce in size to form arterioles, which feed into the capillaries. The capillaries group together form together to form venules which merge into veins to carry blood back to the heart. Arteries and Veins Differences Artery and veins have the same 3 layers, this can differ in thickness and composition depending on vessel type. The innermost layer is the tunica intima, it contains delicate endothelial cells which minimise friction due to their smoothness. The tunica intima layers in arteries also have layers of elastic fibres to help with dimension and recoil. The middle layer is known as the tunica media which is made of elastic and smooth fibres which allow for vasoconstriction/ dilation. This layer is much thicker in arteries. The outermost layer is the tunica externa and is constructed from connective tissue. These fuse with adjacent tissue to anchor the vessel. Elastic Arteries These are the largest arteries in the body and include the aorta and pulmonary truck (heart arteries). They contain a high proportion of layered elastic fibres in the tunica media. They help move blood away from the heart as the walls are distended during ventricular systole (contraction/ squeezing). They recoil during ventricular diastole (relaxation/ dilation). Distension can be felt as a pulse near skin surface. Elastic arteries function as pressure reservoirs. The stretched elastic fibres store mechanical energy momentarily which converts to kinetic energy used to push the blood forward when artery recoils. Muscular Arteries Muscular arteries are distributing arteries, they have greater ability of vasoconstriction and vasodilation. The tunica media contains more smooth muscle fibres and less elastic fibres. They circulate blood through continuous partial muscle contraction, this is known as vascular tone. It helps maintain the pressure and blood flow and can be modulated to shunt blood to specific areas (digestive system or skeletal). Arterioles The smallest arteries, with 1-2 layers of smooth muscle cells. There are around 400 million in the human body. Metarterioles regulate the blood flow across capillary networks, they contain sphincter muscle that contract and relax to control blood flow. Capillary Types The smallest blood vessel, about 20 billion in the body. It provides a huge surface area to aid diffusion of gases, nutrients and wastes. There are no tunica media or externa, its just a layer of endothelial cells with a basement membrane. They are more numerous in metabolically active tissues. There are 3 main types of capillaries: Continuous capillaries are most numerous and are found in the CNS, lungs, muscle and skin. The endothelial cells form a continuous tube. Fenestrated capillaries are found in kidneys, small intestine villi, choroid plexus in the brain, ciliary process of the ye and endocrine glands. Endothelial cells have small holes called fenestrations. Sinusoid capillaries are found in the liver, red bone marrow, the spleen, anterior pituitary, adrenal glands and parathyroid. They have larger diameter compared to other capillaries and can have very large fenestrations. They have little to no basement membrane and have large clefts between endothelial cells. They permit the page of large proteins and blood cells. Blood Flow and Blood Pressure The blood flow is described as the volume of blood that flows through tissue during a specific time, it is measured in mL/min. Total volume of blood pumped by the heart per minute = heart rate x stroke volume. 𝐵 = 𝐻𝑅 × 𝑆𝑉 Haemodynamic is the factors affecting the blood flow. The blood flow is dependent on pressure difference and vascular difference. Blood tends to flow from high pressure areas to low pressure areas, the higher this pressure difference the greater the blood flow. The pressure is produced by ventricular contraction and is highest in the aorta and reduces through vascular system. Normal pressure is taken from brachial artery: systolic = 120mmHg and diastolic = 80mmHg. Averaging these values gives mean artery pressure (MAP). Vascular resistance is caused by friction between blood and the vascular wall, it depends on the lumen size of blood vessel (smaller = greater resistance), the viscosity of blood (viscous = resistance) and length of blood vessel (longer = resistance). Major vasodilators and constrictors Regulating the blood pressure can be done by regulating vascular tone, through vasodilation and vasoconstriction. Vasodilators include epinephrine and norepinephrine (β-2 receptors), nitric oxide, H+ & K+, histamines, heparin and bradykinin and hypoxia (in systemic circuit). Vasoconstrictors include angiotensin II, epinephrine and norepinephrine (α-1 receptors), ADH and hypoxia (in pulmonary circuit). High blood viscosity increases BP. Factors of high viscosity blood include high haematocrit, low deformability of RBCs, high plasma viscosity, high fibrinogen concentration and dehydration. Lecture 5: Tissue Perfusion and Fluid Recovery Capillary Exchange Capillaries are the sight of diffusion of gases, nutrients and waste products. The larger walls of arteries and veins are too thick to permit diffusion. The capillary wall size varies depending on the tissue being perfused. Transport Modes Material is constantly being exchanged between the blood interstitial fluid in the surrounding fluid. This is achieved by diffusion, transcytosis and bulk flow. Diffusion is when oxygen, carbon dioxide, wastes and nutrients travel down their electrochemical gradient passively and into interstitial fluid then into cells. Theres more O2 and nutrients in blood and more CO2 and waste in interstitial fluid. The diffusion pathways are dependent on the material as water soluble material (glucose, amino acids) diffuse through intercellular cleft or fenestrations whilst lipid soluble material (O2, CO2, steroids) pass through capillary endothelial cells. Plasma proteins and red blood cells are too large and can only pass through large intercellular clefts or sinusoid capillaries. Transcytosis is when materials are engulfed by cell membrane inside a vesicle and enter capillary (endocytosis), pinocytic vesicle travels through endothelial cell and exists exocytosis. This is used for transport of insulin and maternal antibodies (igA) to foetus. Bulk flow is when large amounts of material is transported in membrane structure, it is faster then diffusion but relies on concentration gradients as well. Filtration and Absorption Filtration is driven by blood hydrostatic pressure (BHP) which is the blood pressure in vessel and the interstitial fluid osmotic pressure (IFOP) which relies on ratio of solute to solvent. BHP forces fluid out the capillaries into interstitial fluid, pressure of blood pushing against vessel walls. It is about 35mmHg in terminal arterioles and drops to 16mmHg in post capillary venules. Interstitial fluid pushes fluid from interstitial space into capillaries, very small about 1 mmHg. Reabsorption is driven by blood colloid osmotic pressure (BCOP) which is created by albumin in blood. Osmotic pressure primarily driven by plasma proteins, the blood colloid osmotic pressure attracts water from interstitial space into blood, about 26mmHg. The interstitial fluid osmotic pressure draws water from the blood into interstitial space, extremely small. Balance between filtration and absorption is known as net filtration pressure (NFP). This pressure dictates the movement of fluid and solutes and whether volume of blood and interstitial fluids stay the same. Starling’s law of the capillaries states volumes reabsorbed are similar to those filtered. Blood and interstitial fluid volumes remain the same. When lymphatic vessels are blocked or absent, lymphedema occurs, the legs swell and become tight and heavy. Venus return is the blood flowing back from the periphery to the right atrium of heart. The blood hydrostatic pressure in post capillary venules is about 16mmHg. The valves in veins help return blood alongside pumping of skeletal muscles and respiratory pump. Reperfusion/ Reoxygenation Injury Reperfusion is the tissue damage caused by restoration of blood following ischemia/ hypoxia, it is usually blocked due to artery limiting blood flow. Hypoxia leads to an increase in inflammation which is driven by NF-kB and COX-2 pathway. Hypoxia causes a drop in ATP production hence leads to loss of aerobic respiration and cells are unable to meet ATP demand. Biggest user of ATP in the cell are sodium and potassium pumps, less ATP means loss of pump function and the sodium can build up inside the cells alongside calcium buildup. This increase in intracellular solutes attracts water molecules through osmosis. The cells greatly swell and cause modification to rough endoplasmic reticulum and ribosomes which reduces protein synthesis. This leads to a reduction of powerful antioxidants such as superoxide dismutase and catalase. When blood flow is restored, the oxygen creates a huge increase in superoxide radial production which includes free radicals, H2O2, OH and oxidative stress. Oxidative stress causes damage to cell membranes, proteins and DNA. It can cause apoptosis and subsequent loss of function. It is a major cause of injury in cardiac arrest, stroke and diabetic foot ulcer patients and negatively impacts the success of organ transplants. Lecture 6: Blood Volume and Pressure Regulation Regulation of Blood Volume and Pressure To achieve ideal tissue perfusion, blood pressure must be maintained correctly. It is directly related to blood volume due to closed vascular circuits. Regulation of the blood pressure is complex and involves heart rate, stroke volume, vascular tone and blood volume. Limbic System The limbic system is involved with the emotional and behavioural responses. Anticipation at the start of exercise involved signals from the limbic system to the CV centre in the medulla oblongata. The proprioceptors detect increased movement of joints and muscles and send information to the CV centre. Then the heart rate and blood pressure increase. Baroreceptors Baroreceptors are pressure receptors which detect changes in BP. It is found in the aorta, internal carotid arteries and large arteries in the neck and chest. If the BP rises, the baroreceptors stretch more. This information is sent to the CV centre which then will increase the parasympathetic stimulation of the heart via Vagus nerves (decreased heart rate). If the blood pressure falls, less stretch is detected by the baroreceptors, and the signal is sent to CV centre. The CV centre decreases parasympathetic activation and increases sympathetic stimulation of the heart via cardiac accelerator nerves. Epinephrine and norepinephrine are secreted from the adrenal medulla to make heart beat faster with more force. Chemoreceptors Chemoreceptors are a neural regulation of blood pressure; it measures the chemical composition of the blood and is found close to the baroreceptors. It can detect concentration of O2, CO2 and H+ and send this information to the CV centre. If hypoxia, acidosis or hypercapnia is detected then the CV centre increases parasympathetic stimulation, increases BP and stimulates respiratory centre which increases rate and depth of breathing. Hormonal Regulation in BP Hormones play a major role in the regulation of blood pressure and can achieve modulation by cardiac output, systemic vascular resistance and total blood volume. RAAS (Renin angiotensin aldosterone system) is a complex system that uses a variety kind of intermediaries to achieve water content in blood regulation. When there is a reduction in blood pressure, the decreased perfusion is detected by the juxtaglomerular apparatus in the kidneys, which then secretes renin. The renin converts angiotensinogen to angiotensin I then to angiotensin II by ACE (angiotensin converting enzyme). Angiotensin acts through vasoconstriction where vascular resistance is increased, and BP is raised. It also acts through stimulating the release of aldosterone from the adrenal cortex. As aldosterone is a mineralocorticoid it increased sodium and water reabsorption in the kidneys, water then raises blood volume and pressure. Catecholamines are secreted from the adrenal medulla by sympathetic nervous system stimulation. This then raises blood pressure by raising heart rate and contraction force, constricting arterioles near skin and organs and vasodilates arterioles near heart and skeletal muscle. Antidiuretic Hormone (ADH) is produced by the hypothalamus and secreted from the posterior pituitary. It is secreted in response to dehydration or low blood volume. ADH acts as a vasoconstrictor and therefore increases vascular resistance and BP and it increases reabsorption of water from kidney tubules, which increases water volume and BP. Atrial Natriuretic Peptide (ANP) is secreted by cells existing in the atria (who are receptive to stretching). ANP can reduce blood pressure by promoting vasodilation and increasing sodium excretion from kidneys (causes water loss). Modulating Stroke Volume Cardiac output = heart rate x stroke volume per minute An increase in stroke volume can also increase the cardiac output. - End-diastolic volume: Volume of blood once the ventricles have fully relaxed (diastole) and filled with blood - typically around 120 ml - End-systolic volume: Volume of blood that remains in the ventricles after ventricular contraction (systole) – typically around 50 ml - Stroke volume: Volume of blood pumped out of the ventricles during systole - Ejection fraction: The percentage of the end-diastolic volume ejected during systole – normally 60% Heart Volume A resting heart pumps approximately 60% of end diastolic volume (stroke volume, around 70ml). Therefore 40% remains in each ventricle (end systolic volume, 50mL). The factors influencing stroke volume is preload, contractility and afterload. Preload Preload describes the degree of stretch of cardiac muscle fibres prior to contraction, the higher the preload the greater the force of muscle fibre contraction. This concept is like a rubber band stretching and recoiling. Preload is proportional to the end diastolic volume where ventricles fill with more blood as ventricular walls undergo greater stretch and increased volume. End diastolic volume depends on duration and venous return. The duration of ventricular diastole reduces as heart rate increases which leads to reduced blood flow into ventricles and lower end diastole volume. If the venous return increases, more blood flows into ventricles and end diastolic volume is increased. Aerobic exercises increase venous return, increases preload and stroke volume and results in a lower heart rate. Contractility An inotrope is a substance that affects heart contractility. Higher contractility will increase the stroke volume. A positive inotropic agent increases contractility whilst a negative inotropic agent reduces contractility. In cardiac muscle fibre activation, calcium plays a crucial role in activation and calcium can be increased by positive inotropic agents. Positive agents included epinephrine, norepinephrine, dopamine and digitoxin from digitalis plant. Negative agents include beta blockers, acidosis, anoxia, high interstitial K and calcium channel blockers. Afterload Blood is ejected from each ventricle when the pressure exeecds that in the pulmonary trunk and aorta during systole. Pulmonary trunk diastolic blood pressure is about 20mmHg and aorta diastolic BP about 80 mmHg. These two pressures force the semilunar valve closed. After load is the pressure that must be achieved by the blood in the ventricles to open the semilunar valves. Increased afterload reduces the stroke volume and increases end systolic volume. Hypertension (high BP) increases the afterload. The blood diastolic pressure is greater than 80 mmHg in aorta, the left ventricle must generate more pressure and thus the semilunar valve takes longer to open. Atherosclerosis also increases afterload. Hypertension (High BP) It is a major cause of diseases around the world which affects about a billion people. The risk factors include age, race, inactivity, smoking, high sodium diet and alcohol intake. Pharmacological interventions to reduce hypertension: ▫ ACE inhibitors (inhibit formation of Ang II and aldosterone) ▫ Beta blockers (reduce sympathetic system influence on heart) ▫ Diuretics (reduce blood volume) Lecture 7: The Respiratory System Organisation of the Respiratory System The respiratory system is responsible for facilitating the gas exchange of gases between the air we breathe; blood and cells require oxygen and filter out carbon dioxide. Most energy is produced aerobically which is much needed due to the human size and complexity. There is a constant need for oxygen by mitochondria for ATP production and a constant need of carbon dioxide clearance to prevent acidosis. The respiratory system can be divided into the upper and lower tracts. The upper tract includes nose and nasal cavity, the pharynx and larynx whilst the lower tract includes the trachea (windpipe), bronchial tubes and alveoli. Major Components The Nose and Naval Cavity The external nose is constructed from bone and hyaline cartilage and is lined with a mucus membrane. It is divided internally by the nasal septum and has two openings are known as the external nares or nostrils. The olfactory receptors are located in the olfactory epithelium in the roof of the nose/nasal cavity which permit the reception of odorants. The function of this is to warm the air, prevent dehydration, trap particles via the mucous membrane and propel bad particles towards pharynx via cilia. The Pharynx The pharynx is posterior to the nasal cavity and extends to the larynx. It has 3 regions, the nasopharynx, oropharynx and laryngopharynx. It also contains the openings of the auditory tubes which are known as pharyngotympanic tubes or eustachian tubes, it is linked to the middle ear and equalises air pressure. The pharynx is constructed of skeletal muscle and is circular and longitudinal, its contraction is involved in swallowing (deglutition). It is lined with mucous membrane and contains the tonsils (palatine and lingual). The tonsils play a role in immunity and can be subject to inflammation. They are patches of lymphatic tissue like lymphatic nodes. The Larynx It is connected to the pharynx and links it with the trachea. It is constructed from 9 sections of cartilage. It contains the vocal folds for speech and the epiglottis, which is a leaf-shaped elastic cartilage that closes off the glottis to prevent food or fluid from entering the trachea during swallowing. The Trachea The trachea is a tubular windpipe extending from the larynx to the two primary bronchial tubes. It is constructed from 4 layers. The mucosa is the innermost layer and contains pseudostratified ciliated epithelium which traps particles by the mucous and propels it by cilia for swallowing. The submucosa is mostly areolar (loose) connective tissue which contains mucus-secreting glands and their ducts. The hyaline cartilage has16-20 incomplete cartilage rings, the open portion faces posteriorly towards the oesophagus. The adventitia is a connective tissue outer layer. The Bronchial Tube The trachea divides into the two primary bronchi, each primary bronchus feeds air into and out of the left/right lung. It is lined with pseudostratified ciliated epithelia and also has incomplete cartilage rings. The carina is the lower internal ridge where the right and left bronchi originate, they are very sensitive and triggers cough reflex. These primary bronchi divide into secondary or lobar bronchi and each secondary bronchus feeds a single lobe of the lung. These then further divide into tertiary or segmental bronchi then the smaller bronchioles. The smallest bronchioles are known as terminal bronchi. The branching of bronchial tubes is known as the bronchial tree The Bronchial Tubes Epithelium Changes Primary, secondary and tertiary bronchi Pseudostratified ciliated columnar epithelium with goblet (mucus secreting) cells Large bronchioles Simple ciliated with some goblet cells Smaller bronchioles Simple ciliated with few goblet cells Terminal bronchioles Simple cuboidal As bronchial tubes get smaller, plates of cartilage replace incomplete rings and the smooth muscle content increases as cartilage decreases. Smooth muscle is present in spiral bands which helps keep bronchial tubes open and are influenced by catecholamines. The smooth muscle causes bronchodilation through the influx of epinephrine and norepinephrine. Sometimes muscle spasm can close off the bronchial tubes (asthma attack). Structure of Airways and Alveoli The Lungs The lungs are paired organs that sit inside the thoracic cavity (lined by parietal pleura), surrounded by the heart. The left and right lung reside in separate double-walled structures called pleural membranes. There is a visceral pleura which covers the lungs. Small spaces exist between these layers known as the pleural cavity which contains lubricating fluid to allow smooth inflation and deflation of the lungs. The Alveoli The terminal bronchioles represent the end of the conducting zone of the lung. These are the structures that carry air into and out of the lung and each terminal bronchus gives rise to multiple respiratory bronchioles. The terminal bronchus is the start of the respiratory zone of the lung and contains clusters of inter-connected hollow spheres called alveoli. The alveoli extent from an alveolar duct that is contiguous with each respiratory bronchus. Each alveolus is covered in pulmonary capillaries for gas exchange. It is also covered in elastic fibres that stretch during inspiration and recoil to aid exhalation. There are macrophages on the inner surface instead of cilia or mucous. Alveoli are constructed using simple squamous epithelial cells (I cells). The alveolar wall and capillary wall form the respiratory membrane where gases diffuse across. It is very thin to aid diffusion speeds (0.5 μm). It also contain type II cells (septal cells) which are small cuboidal cells with microvilli that secrete alveolar fluid (reduces surface tension). Gas Exchange Efficiency The ultra-thin respiratory membrane ensures the shortest distance gases must travel between the inside of the alveoli and the blood. The lungs contain around 300 million alveoli with a large surface area. This combination of thin respiratory membrane and large surface area ensures rapid gas diffusion rate. Lecture 8: Pulmonary Respiration Air Pressures and Pulmonary Ventilation Pulmonary ventilation is the delivery of oxygen rich air to the alveoli and the expelling of carbon dioxide rich air to the atmosphere. This requires specific skeletal muscles and is monitored by nervous systems. The movement of air into and out of our lungs is dependent on different air pressures (atmospheric air pressure and pressures inside our lungs). Air movement follows Boyle’s law, which is concerned with the association of the pressure and the volume of a gas. Pressure is inversely proportional to volume. There is a third pressure called the intrapleural air pressure which is the pressure in the pleural cavity. Boyles Law The main premise of Boyle’s law is that if the volume of a gas is increased, its pressure reduces and vice versa where the volume of a gas being reduced, its pressure increases. Our respiratory muscles make our lungs into a type of pump and by increasing their volume, the air pressure reduces. By reducing their volume, the air pressure increases. Boyle’s Law: P1V1 = P2V2 Intrapulmonary or alveolar pressure the force exerted by gases within the alveoli. To inflate our lungs with external air, we must reduce the air pressure within them to increase volume. To exhale we must increase alveolar air pressure by reducing the lung volume. Air is expelled from our lungs once alveolar air pressure is greater than atmospheric air pressure. Respiratory Muscles for Pulmonary Ventilation There are specific structures to increase and decrease our lung volume. The ribcage: the ribs can pivot and move upwards and outwards. The skeletal muscles; includes the diaphragm, external intercostals, internal intercostals and the abdominals, obliques, scalenes and sternocleidomastoid. The Diaphragm The diaphragm is a dome-shaped muscle that forms the lower section of the thoracic cavity. It flattens around 1 cm during quiet breathing and can flatten up to 10 cm during strenuous breathing. Its contraction contributes about 75% of inhaled air. The External Intercostals The external intercostals raise and widen the rib cage and contributes about 25% of inhaled air. Lung Volumes and Capacities Alveolar Surface Tension Alveolar surface tension affects pulmonary ventilation as water molecules are bound by hydrogen bonds. There is a stronger attraction to each other than to gas molecules in the air which causes the surface tension to pull the alveoli slightly inwards and reduce their volume. The surface tension must be overcome to expand the volume of each alveolus and there is a surfactant secreted by Type II cells to help reduce this. Lung Compliance Lung compliance describes the ease of lung expansion which is caused by the difference between intrapleural and alveolar pressures. High compliance means it is easy to expand per unit change of pressure, but low compliance means it is difficult to expand per unit change of pressure. Low compliance may be caused by: - Scarring of alveoli usually caused by diseases such as tuberculosis - Increased fluid in lung tissue – pulmonary oedema - Deficiency of surfactant – increased surface tension Airway Resistance Airway resistance is the resistance caused by walls of the bronchial tubes. They are normally dilated during inhalation and constrict slightly during exhalation. The airway resistance is modulated by the ANS. Any narrowing or obstruction to airways increases the resistance as seen in asthma and chronic bronchitis. Respiratory Rates Adults average about 12 breaths per minute, which moves about 500 mL of air per breath. The respiratory rates are adaptable to the demands of oxygen by the body and the volume of air can increase by 50 x during peak exercise over resting values. The volume increases per breath and the number of breaths per min increases. Lung Volume The total volume of the lungs can be divided into residual volume, tidal volume, inspiratory reserve volume and expiratory reserve volume. The residual volume is the volume of air remaining in lungs after forced expiration as not all air gets expelled from the lungs. The tidal volume is the resting volume of air inhaled and exhaled, it represents air moved in one breath. Inspiratory reserve volume is the excess volume inhaled beyond the normal tidal volume and is achieved during deep inhalation. Expiratory reserve volume is the excess volume exhaled beyond the normal tidal volume and is achieved during deep expiration. Lung Capacity The combination of different lung volumes can be used to determine the lung function. The inspiratory capacity is the inspiratory reserve volume + tidal volume. It is the maximum volume of air inhaled from normal expiratory level. The functional residual capacity is the expiratory reserve volume + residual volume. It is the volume of air remaining in lungs after normal expiration. The vital capacity is the inspiratory reserve volume + tidal volume + expiratory reserve volume and represents the maximum volume of air that can be inhaled/exhaled. The total lung capacity is the vital capacity + residual volume. CNS and PNS in Breathing Regulation Breathing Control There are two clusters of neurons that are responsible for breathing: - Medullary respiration centre in the medulla oblongata - Pontine respiratory group in the pons They are collectively known as the respiratory centre. Breathing Regulation Breathing rate and depth can be influenced by other regions of the CNS and PNS. We can voluntarily hold our breath Stimulation is achieved by the hypothalamus and limbic system in response to emotions inducing laughing a or crying. There are receptors detect that the concentrations of CO2, O2 and H+ and initiate changes to breathing. Lecture 9: Gas Exchange Partial Pressure of Gas Air Pressure Air pressure is created by the earth’s gravitational pull on the air around and above us. The atmospheric pressure at sea level is 760 mmHg (101.325 kPa or 1 atm) and reduces as we increase altitude as there is less air being pulled down. At around 5,500 m, air pressure is approximately half that at sea level (380 mmHg). Gas Importance As aerobic organisms, humans consume large quantities of oxygen especially during ATP production and produce CO2 that must be eliminated as higher CO2 concentration increases H2CO3 formation and reduces blood pH. Partial Pressure The partial pressure is the individual contribution to the total atmospheric air pressure. Dalton’s Law states that the total air pressure is the sum of the partial pressures of all gases in a mixture. Hence, partial pressures can be calculated by knowing the total air pressure and the percentages of the gases in the mixture. Atmospheric Gas Percentage (%) Partial Pressure (mmHg) N2 78.6 597.4 O2 20.9 158.8 Ar 0.093 0.7 CO2 0.04 0.3 H2O and others 0.367 2.8 Total 100% 760 mmHg *at sea level Partial Pressure of Oxygen = 20.9% of 760 mmHg = 159 mmHg Partial Pressure of Carbon Dioxide = 0.04% of 760 mmHg = 0.3 mmHg Gas Solubility in the Respiration System Partial pressures of gases are important in our respiratory system as simple diffusion is used to transport gases from the alveoli and diffusion is reliant on concentration gradients. The solutes diffuse from a high concentration to a lower concentration and higher gradients = faster diffusion rates. Therefore, the partial pressure of oxygen must be higher in the alveoli compared to blood in the pulmonary capillaries to ensure the oxygen diffuses into blood. Similarly, the partial pressure of carbon dioxide must be higher in pulmonary capillary blood compared to the alveoli to ensure carbon dioxide diffuses out of blood and into our lungs. Henry’s Law Henry’s law is when a gas is in contact with a liquid, the dissolved gas is proportional to its partial pressure and solubility. A high partial pressure and solubility will increase the amount of gas dissolved in solution whilst a low partial pressure and solubility will cause a decrease in gas dissolved in solution. The fizz in champagne is caused by CO2 in the liquid, created either by yeast fermentation or injected under high pressure. The PCO2 in a champagne bottle neck is around 3800 mmHg which keeps the fizz in the wine. When opening, the CO2 escaping from the bottle neck can be heard because the partial pressure of CO2 in the atmosphere is very low (0.3 mmHg), it comes out of the solution as bubbles. This continues until the partial pressures in the atmosphere and in the wine have equalised. Solubility of O2 and CO2 The principles of Henry’s law are dependent on a gas’s solubility. O2 has poor solubility in water due to the non-polar nature of its molecular structure and CO2 is 24 times more soluble in water. CO2 is slightly polar in certain regions and so interacts with the +ve and –ve regions of water molecules. It combines with H2O molecules to form H2CO3 and hence CO2 forms a solution with water more readily. Partial Atmospheric Alveolar Air Pulmonary Systemic Tissue Cell Pressure Air Capillary Capillary Blood Blood PO2 159 mmHg 104 mmHg 40 mmHg 100 mmHg 40 mmHg PCO2 0.3 mmHg 40 mmHg 45 mmHg 40 mmHg 45 mmHg *In Respiratory System, differences occur due to small tidal volume used in quiet breathing, O2 constantly diffusing into blood and CO2 high in residual and expiratory reserve volumes. O2 and CO2 Transport Oxygen Transport As oxygen has poor solubility in water only around 1.5% dissolves in plasma. The other 98.5% binds to haemoglobin in red blood cells. Each haemoglobin molecule contains four haem units and each one binds one O2 molecule. When O2 is bound to haemoglobin, it is known as oxyhaemoglobin. Haemoglobin Dynamics The binding of oxygen to haemoglobin is easily reversable. The haemoglobin that is fully converted to oxyhaemoglobin is said to be fully saturated, the saturation is dependent on the PO2. The oxygen- haemoglobin dissociation curve is a plot between PO2 and oxyhaemoglobin saturation. Oxyhaemoglobin Saturation There are many other factors that influence oxyhaemoglobin saturation, including acidity, PCO2 and temperature. The binding of oxygen to haemoglobin decreases with acidity (Bohr effect). Hydrogen increases causes oxygen to dissociate from haemoglobin and this is advantageous in tissues with a high H+ concentration as it increases oxygen unloading. When carbon dioxide partial pressure is increased, the binding of O2 is decreased. Instead, the CO2 binds to haemoglobin forming carbaminohaemoglobin. When the temperature is increased, the heat reduces oxygen binding to haemoglobin. CO2 Transportation CO2 is transported in the blood in three ways: Bicarbonate ions (HCO3) accounts for around 70% of CO2 transport and is present in plasma and produced by carbonic anhydrase (CA). CO2 + H2O → CA → H+ + HCO3- This reaction reverses in pulmonary capillaries and CO2 is exhaled. Carbamino compounds accounts for 23% of CO2 transport. The CO2 binds to amino groups of amino acids to form carbaminohaemoglobin. This reaction is promoted by high PCO2. Hb + CO2 → Hb - CO2 The dissolved CO2 in plasma accounts for the last 7% of CO2 transportation. Lecture 10: Ventilation, Perfusion and Airflow Control Ventilation is air flow into the alveolus. Perfusion is blood flow through the pulmonary capillaries. Ventilation/ Perfusion Ratio Some alveoli receive more air that others during inhalation, usually the ones at the base of the lungs receive more air while the top receives less air (about a 50% difference). This distribution occurs due to the weight of fluid in the plural cavity being greatest at the base due to gravity. The gravity increases intrapleural pressure. Therefore, the alveoli are less expanded but have higher compliance and can be filled with more air. The respiratory zone in the lungs includes respiratory bronchioles, alveolar ducts (controls air flow to alveoli), alveolar sacs and the alveoli. 𝑉 Ratio of ventilation to Perfusion: 𝑄 - Base: 0.3 Apex: 2.1 Centre: 1 The volume of blood pumped through the pulmonary circuit is the same as the systemic circuit but the dynamics are different in each system. The aystemic circuit is a high pressure system where vascular resistsance regulated blood flow. The pulmonary circuit is a low pressure system that has parallel pathways for blood flow and low vascular resistance. Physiological Response to Ventilation/ Perfusion Ventilation and Perfusion can both be modulated and regulated to improve the efficiency of respiratory gas exchange. The aim is to math the ventilation and perfusion rates to increase the potential for maximum gas exchange. When there is low alveolar oxygen content: vasoconstriction occurs to limit the blood flow to alveoli. The blood is shunted and moves to alveoli with more oxygen. The bronchioles dilate to increase air flow and oxygen. When there is high alveolar carbon dioxide content: the bronchioles dilate to increase air flow to increase carbon dioxide and oxygen diffusion. Pulmonary Disorders Restrictive pulmonary disorders: Pulmonary fibrosis When normal lung tissue is replaced by fibrotic tissue, the lung compliance is reduced and oxygen diffusion is inhibited. This is often caused by autoimmune disorders such as tuberculosis, asbestosis and silicosis. Restrictive pulmonary disorders: Pulmonary oedema This is commonly caused by heart problems: Congestive heart failure is when the left ventricle/ AV valve is dysfunctional and blood fills on the left side as it cannot be pumped into systemic circuit. This increases pressure of pulmonary blood vessels which forces fluid out to collect in alveoli. Hypertensive crisis is when the left ventricular stroke volume is inhibited by increased afterloads. Damage to pulmonary capillary membranes makes capillaries more permeable to fluid. This can be caused by infection like pneumonia or inhalation of toxic gases. Obstructive pulmonary disorders: Asthma Asthma is the chronic inflammation of the bronchial tubes and is characterised by bronchospasms, increased mucus secretion and airway obstruction. It caused by genetic and environmental factors including allergens, pollutants, drugs and preservative sulphates. Obstructive pulmonary disorders: Chronic bronchitis Chronic bronchitis is an inflammatory condition resulting in excess thick mucus secretion, loss of ciliary function and increased risk of infection. Obstructive pulmonary disorders: Emphysema Emphysema causes loss of alveolar walls which means there are large spaces of leftover air and new oxygen rich air cannot enter the lungs., Masses: Tumours or scar tissue This is when large masses block the airways, including tumours or scar tissue. Bronchoconstriction and Dilation Air flow functions like blood flow in which pressure difference drives the flow and there is resistance in airway walls. A 10% reduction in airway radius can lead to a 52% increase in resistance and 35% decrease in airflow. Flow = Pressure gradient / Resistance Modulators of Airway Diameter Within the airways, the smooth muscle contains receptors for neurotransmitters and hormones. Bronchoconstriction is caused when muscarinic receptors bind to acetylcholine and bronchodilation is caused by B adrenergic receptors binds to adrenaline (epinephrine). Lecture 11: Respiration inBalance and System Integration pH is the power/ potential of hydrogen and refers to a scale of hydrogen concentration in fluids. The body needs a pH of 7.35 - 7.45 in order to maintain homeostasis in the body and when pH is below 7.35, acidosis occurs and above 7.45 alkalosis occurs. Acidosis Effect on the Body Acidosis results in the depression of the central nervous system which is caused by synaptic transmission loss. When the pH is below 7, disorientation, coma and death can occur. Respiratory acidosis is when there are high carbon dioxide concentrations (above 45 mmHg) and more H2CO3 is formed and/or when ventilation and perfusion does not remove CO2. This can be caused by lung diseases, respiratory muscle damage, innervation and drugs. Metabolic acidosis is when working cells produce too much acid and kidneys fail to remove hydrogen from the blood. This s caused by kidney diseases, diabetic acidosis (ketoacidosis), lactic acidosis, bicarbonate ion loss from diarrhea and poison. Alkalosis Effect on the Body Alkalosis causes overexcitement of the central and peripheral nervous systems which leads to nervous feelings, muscle spasms, convulsions and death. Respiratory alkalosis is when blood PCO2 is too low (below 35 mmHg) and less H2CO3 is formed. This is caused by hyperventilation (too much removal of CO2). Metabolic alkalosis is when there is high systemic blood concentration of HCO3 and acidity is reduced. This is caused by drugs (sodium bicarbonate) and vomiting (gastric acid loss). Blood pH Maintenance There are 3 methods to regulate pH. A buffering system is rapid but does not remove Hydrogen. Increasing pulmonary ventilation rates and depth removes excess carbon dioxide. Excretion of hydrogen by kidneys is slowest but is the only way to remove hydrogen from the body. Carbon Acid-Bicarbonate Buffering System When the pH drops and hydrogen concentration increases, bicarbonate ions are used to bind free hydrogen and remove it as carbon dioxide in exhalation. Carbonic acid (H2CO3) acts as a weak acid and bicarbonate ions (HCO3) acts as a weak base. 𝐻 + 𝐻𝐶𝑂3 → 𝐻2𝐶𝑂3 → 𝐻2𝑂 + 𝐶𝑂2 Hydrogen Ion + Bicarbonate Ion → Carbonic Acid → Water + Carbon Dioxide When the pH increases: 𝐻2𝐶𝑂3 → 𝐻 + 𝐻𝐶𝑂3 Respiratory System and Cardiovascular System Cooperation Cooperation between these systems is necessary as they rely on each other to achieve their primary goals of oxygen deliver and carbon dioxide removal. During exercise more oxygen is consumed, and more carbon dioxide is produced. To counteract this, pulmonary ventilation and perfusion increases. Vasodilation occurs to increase blood flow and partial pressures drive diffusion for respiration. Anticipating exercise stimulates increased breathing rate and depth as driven my limbic system. The breathing pattern is then dependant on exercise intensity and regulated by chemoreceptor feedback which measures partial pressure of oxygen and carbon dioxide and hydrogen levels. Furthermore, pulmonary perfusion is increased as cardiac output increases in both circulatory systems. This increases the oxygen diffusion capacity by 3x as pulmonary capillaries are fully perfused. Ageing and the Respiratory System As humans age, the respiratory system is negatively impacted. The airways lose elasticity and alveoli becomes baggy. The chest becomes more rigid. Bronchial tube ciliary function is loss and alveolar macrophage reduction leads to increased risk of infection and disease. Vital capacity has a 35% loss. Lecture 12: Energy Metabolism I Metabolism Metabolism is the collection of all cells having their own chemical reactions to regulate their own internal environments. The objective of metabolism is to break down food for energy (mainly carbs and lipids). New molecules/ proteins/ nucleic acids/ lipids/ carbs are formed from food breakdown. There are also processes to eliminate cellular waste. There are two metabolic categories. Catabolism which involved the breaking down of complex molecules to simpler ones. They are generally exergonic ad release more energy than they consume. Anabolism which involve building larger structures from simpler ones which is an endergonic reaction. An example of an anabolic reaction is ADP and P forming ATP. These metabolic reactions are balanced between catabolic and anabolic. Structure of ATP ATP (adenosine triphosphate) provides most of the energy required for metabolic reactions in the cell. Each cell contains 1 billion molecules of ATP which each last less than 1 minute hence the need for constant ATP production. Oxidation and Reduction Oxidation and reduction reactions result in a change to the original molecule or substance. Oxidation can occur by adding oxygen together, removing electrons from atom/molecule or the removal of hydrogen. Reduction can occur by the removal of oxygen, the addition of electrons (forms high energy electrons) and the addition of hydrogen. The redox cycle is when the oxidative and reduced states occur simultaneously. NAD and FAD NAD: Nicotinamide adenine dinucleotide. FAD: flavin adenine dinucleotide NAD and FAD are essential cofactors that help in transferring electrons and hydrogen atoms in metabolic reactions, which is crucial to produce ATP. They both have an oxidized and reduced state. When they are oxidised, they release the hydrogen and electrons. Oxidative Phosphorylation Oxidative phosphorylation is a process where energy from electrons is used to produce ATP. This involves the oxidation of substrates (such as glucose or fatty acids. These electrons are then transferred through a series of proteins and molecules embedded in the inner mitochondrial membrane, collectively known as the electron transport chain (ETC). The folded inner membrane (cristae) increasing the surface area. Electrons are supplied by the two main products of the Krebs cycle – high-energy electron carriers: NADH and FADH2. At the end of the electron transport chain, oxygen combines with the electrons and hydrogen ions to form water (H₂O). The energy released from the electrons moving through the ETC is used to pump protons across the mitochondrial membrane, creating a proton gradient. This gradient drives the enzyme ATP synthase to produce ATP from ADP (adenosine diphosphate) and inorganic phosphate. Glucose Glucose is the preferred energy substrate for ATP production, or even fructose and galactose. This glucose can be oxidised to form ATP. Orit can be metabolized and form amino acids, glycogen and triglycerides. Glucose enters cell through GluT (glucose transporters), this is facilitated diffusion. Once inside the cell, glucose is phosphorylated which stops it from leaving. Glucose Catabolism Glucose catabolism involves a 3 stage cycle of glycolysis, formation of acetyl coenzyme A and Krebs cycle reactions. Glycolysis Glycolysis is a crucial metabolic pathway that converts glucose into pyruvate in cytosol while producing a small amount of ATP and NADH. One molecule of glucose (C6H12O6) is oxidised to produce: - 2 molecules of ATP - 2 molecules of pyruvic acid - 2 molecules of reduced NAD (NADH) Acetyl Coenzyme A formation This is the intermediate stage that oxidises the pyruvic acid for entry into the Krebs cycle. In mitochondria, pyruvic acid produces: - 1 molecule of CO2 - 1 molecule of reduced NADH + H+ - 1 molecule of acetyl coenzyme A The Krebs cycle Acetyl CoA is oxidised in the mitochondrial matrix and its aim is to produce NADH and FADH2. These are used in the ETC. Krebs cycle also produces a bit of ATP and CO2. Electron Transport Chain Reactions A series of electrons are carried down the inner mitochondrial membrane. There are 1000s of transport chains per mitochondria as the folded membrane (cristae) increases the surface area. The carriers are systematically reduced and oxidised and the last electron acceptor is O2. Electron carriers are proteins found in the inner mitochondrial membrane and are known as protein complexes I – IV. They contain two key additional factors: Coenzyme Q10 and Cytochrome C complex. The electrons are supplied by the two main products of the Krebs cycle – high-energy electron carriers: NADH and FADH2. NADH is oxidised and donates 2 electrons to protein complex I. The electrons are passed between the other complexes and as this happens, each protein complex pumps hydrogen ions (protons) into the intermembrane space – 10 in total. - Complex I pumps out 4 protons - Complex III pumps out 4 protons - Complex IV pumps out 2 protons FADH2 is oxidised and donates 2 electrons to protein complex II which is then passed to coenzyme Q10 and then on to complex III and IV. Again, protons are pumped but complex I is missed so only 6 protons are pumped into the intermembrane space. - Complex III pumps out 4 protons - Complex IV pumps out 2 protons ATP Production The protons pumped by the protein complexes collect in the intermembrane space which creates a high concentration gradient of H+. The protons pass down their electrochemical gradient and into the matrix through the final protein (ATP synthase/synthetase). The ATP synthase acts as a generator and the flow of protons powers the phosphorylation of ADP to ATP. Lecture 13: Energy Metabolism II Mechanisms of Glucose Anabolism Glucose is the preferred energy substrate for ATP, this involved glucose catabolism. There are two processes when concerned with glucose anabolism: glycogenesis and gluconeogenesis. Glycogenesis Glucose can be stored in its polysaccharide glycogen form in the liver and skeletal muscle. The total storage amounts to 500g with 75% being stored in skeletal muscles. The process of glycogenesis is driven by the hormone insulin and is actioned when glucose levels drop. Gluconeogenesis The process of gluconeogenesis occurs when glycogen storage is empty, and more glucose molecules are formed in the liver. In this process, proteins and lipids are catabolised. New glucose molecules are made from glycerol (from triglycerides), lactic acid and certain amino acids (alanine and glutamine). Gluconeogenesis is initiated by cortisol (glucocorticoid) and glucagon (from pancreatic alpha cells). Cortisol initiates the catabolism of proteins and increases available amino acids. Thyroid hormones are released which mobilise proteins and lipids. Lipid Metabolism and Lipolysis Lipids are the primary energy storage molecules, 98% of storage being triglycerides. Lipids offer denser energy levels compared to carbs and proteins, and they are hydrophobic, meaning the do noy exert osmotic pressure. They are packed in adipocytes and found in subcutaneous layer / visceral fat. Lipolysis Lipolysis is the process of breaking down stored fat (triglycerides) into fatty acids and glycerol. The fatty acid can be oxidised and be used to produce ATP, and the glycerol is then converted into glyceraldehyde 3-phosphate. The glycerol can be converted into glucose if ATP is high or catabolised to pyruvic acid if ATP is low. Fatty Acids Fatty acids are long hydrocarbon chains that are very energy dense. The catabolism starts in the mitochondrial matrix. Beta oxidation is the process of removing two carbon atoms from the fatty acid at a time. These are attached to coenzyme A to form acetyl coenzyme A(acetyl CoA). Fatty Acid Catabolism After lipolysis has occurred, fatty acid catabolism can occur which is a process of converting fats into usable energy for the body. Activation: Free fatty acids are converted into fatty acyl-CoA in the cytoplasm, using ATP. Transport: Fatty acyl-CoA is transported into the mitochondria with the help of the carnitine shuttle system. Beta-Oxidation: Inside the mitochondria, fatty acyl-CoA is broken down into acetyl-CoA units through a series of reactions, producing FADH₂ and NADH. Acetyl-CoA Utilization: Acetyl-CoA enters the krebs cycle to generate ATP, NADH, and FADH₂, which are used to produce more ATP. Ketogenesis (if needed): Excess acetyl-CoA can be converted into ketone bodies for use as an alternative energy source. Fatty acid Types Fatty acids can be classified in many ways but are most classified by whether they are saturated or unsaturated and/or the length of the hydrocarbon chain. These factors are important to our health and wellbeing as oxidised fatty acids are involved in the development of atherosclerosis and lipid-derived inflammatory mediators are dependant of the type of fatty acid. Saturated fatty acids have more hydrogen atoms, single covalent bonds and no CC double covalent bonds. Unsaturated fatty acids have one (monosaturated) or more (polysaturated) double covalent bonds. The end of the carbon chain is called omega. The number (i.e. omega 3 or omega 6) is the number of carbons from the omega end where the first double bond occurs. Lipoproteins A lipid anabolic process is lipogenesis, which is the synthesis of lipids. It takes place in the liver and the adipocytes and is initiated by insulin. Lipogenesis occurs in response to a positive energy balance when more energy is consumed than used. Carbs, proteins and fats are converted into triglycerides and stored. Lipid Transport As lipids are non-polar and hydrophobic, they must be encased in a hydrophilic shell before transportation in blood occurs. They are packaged into lipoproteins. This process occurs in the intestines, the intestines package lipids into large lipoproteins called chylomicrons. It can also occur in the liver; it produces very low-density lipoproteins (VLDP) and low-density lipoproteins (LDL). Both the intestines and liver produce high density lipoprotein (HDL). Protein Metabolism Carbohydrates and lipids can be stored in the body. Proteins cannot be stored as they are broken down into amino acids. Excessive amino acids are converted to glucose or triglycerides. Protein Catabolism Protein catabolism is driven mainly by the glucocorticoid cortisol and are broken down into their individual amino acids. The amino acids can then be converted into different amino acids (in some cases), used to construct new proteins, converted to fatty acids, ketone bodies or glucose or oxidised to make ATP (Via conversion to acetyl CoA). Protein Anabolism The human body contains 20 different amino acids and 9 of these are known as essential amino acids which means the body either cannot synthesise them or cannot synthesise enough. Humans can produce between 80,000 to 400,000 different proteins and many are variants of the same protein. This is from around 20,400 protein-coding genes. Protein deamination involves the removal of the amino group from the amino acid in the liver or kidney. Protein transamination involves recycling nitrogen to produce non-essential amino acids and to prevent ammonia production and excretion of nitrogen from kidneys. This uses enzymes called transaminases and results in an amino group transferring to a keto acid. Lecture 14: Digestive System I The digestive system’s main role is to break down food, absorb nutrients and eliminate indigestible material. The digestive system is also home to our microbiome that hosts bacteria that reside in our large intestine which is a huge research area. It contributes to health and disease states via metabolites. Food nutrients: macromolecules (proteins, carbs, lipids, nucleic acids), micronutrients (vitamins, minerals) and water. The 6 Main Functions - Ingestion: Process of placing food in the mouth - Secretion: Release of water, digestive enzymes and acids, salts and buffers into the GI tract - Mixing and Propulsion: Contracts and relaxes smooth muscle, mixes food and secretion and moves content down GI tract. - Digestion: mechanical/ chemical food breakdown, polymers to monomers and epithelium passageway. - Absorption: Describes nutrients and water passage through digestive epithelium and to blood/lymph - Defecation: Removal of wastes, indigestible material, bacteria, dead

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