The Circulatory System 1 & 2 (2023-24).pdf
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WEEK WEEK 26 18 MPharm Programme Normal Systems The Circulatory System 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Circulatory System WEEK Outline of Lecture Series 18 Overview of the components of the circulatory system & their main fun...
WEEK WEEK 26 18 MPharm Programme Normal Systems The Circulatory System 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Circulatory System WEEK Outline of Lecture Series 18 Overview of the components of the circulatory system & their main functions The composition of blood and the main functions of its solute & cellular constituents The gross structure & functional anatomy of the heart Cardiac cell types and their characteristic properties & functions, and the cardiac cycle The gross structure & functional anatomy of the vascular system Regulation of cardiac output & blood pressure Slide 2 of 154 MPharm PHA112 The Circulatory System Learning Outcomes WEEK 18 At the end of this series of lectures, you should be able to: Describe the major components of the circulatory system & their main functions Describe the composition of blood and the main functions of its solute & cellular constituents Describe the location & gross anatomy of the heart Describe the cardiac cell types & their characteristic properties & functions, and the cardiac cycle Describe the structure & function of the various segments of the blood vessel or vascular system Give an account of the mechanisms involved in the regulation of cardiac output & blood pressure Slide 3 of 154 MPharm PHA112 The Circulatory System WEEK 18 Components of the Circulatory System Three basic components Blood Transport medium through which dissolved or suspended materials (e.g. O2, CO2, nutrients, electrolytes, hormones and metabolic wastes) are carried over long distances in the body The Heart Serves as a pump that generates the cardiac output & pressure gradient needed for blood to flow to organs & tissues Blood vessels Complex network of conduits or portals through which blood is carried & distributed from the heart to all parts of the body & back to the heart Slide 4 of 154 MPharm PHA112 The Circulatory System WEEK 18 Functions of the Circulatory System Transportation Respiratory Transports O2 and CO2 Nutritive Carries absorbed products of digestion to the liver, and to organs & tissues Excretory Carries metabolic wastes to kidneys to be excreted Slide 5 of 154 MPharm PHA112 The Circulatory System WEEK 18 Functions of the Circulatory System Regulation Hormonal Carries hormones to target tissues to produce their effects Homeostasis Helps maintain the internal environment, e.g. pH & electrolyte balance, etc Temperature Diverts blood to cool or warm the body Slide 6 of 154 MPharm PHA112 The Circulatory System WEEK 18 Functions of the Circulatory System Protection Haemostasis Mediates blood clotting to prevent bleeding or haemorrhage Immunity Carries leukocytes, cytokines and complement that act to protect against invading pathogens Slide 7 of 154 MPharm PHA112 The Circulatory System WEEK 18 Blood Slide 8 of 154 MPharm PHA112 The Circulatory System Blood WEEK 18 Slide 9 of 154 MPharm PHA112 The Circulatory System Blood WEEK 18 Specialised liquid connective tissue Vehicle for short- & long-range mass transport of materials between cells between cells & the external environment Total volume varies with body size changes in fluid & electrolyte concentration amount of adipose tissue Constitutes ~8% of body weight 5-6 litres (males) and 4-5 litres (females) Slide 10 of 154 MPharm PHA112 The Circulatory System Composition of Blood WEEK 18 Consists of blood cells (formed or cellular elements) suspended in liquid plasma Plasma (~55%) straw-coloured liquid consists of water (~92%) and dissolved solutes specialised proteins (~7%) electrolytes (ions) nutrients, hormones and metabolic wastes Formed or cellular elements (~45%) red blood cells (erythrocytes) white blood cells (leukocytes) platelets (thrombocytes) Slide 11 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 12 of 154 Composition of Blood MPharm PHA112 The Circulatory System WEEK 18 Slide 13 of 154 Composition of Blood MPharm PHA112 The Circulatory System WEEK Composition of Blood 18 Blood 55% 45% Formed elements Platelets Red blood cells (4.8%) (95.1%) Plasma Proteins (0.1%) (92%) Platelets Red blood cells White blood cells (4.8%) (95.1%) (0.1%) Water (92%) Gases (7%) Proteins (7%) Wastes Nutrients Hormones Gases Vitamins Eosinophils Basophils Monocytes (1–3%) (<1%) (3–9%) Neutrophils Eosinophils (54–62%) (1–3%) Slide 14 of 154 Electrolytes Nutrients Basophils (<1%) MPharm Albumins Hormones N2 O2 Globulins CO2 (25–33%) Monocytes Lymphocytes Albumins Globulins (3–9%) (25–33%) (60%) (36%) PHA112 Fibrinogen (4%) The Circulatory System N2 O2 CO2 WEEK 18 Gender Differences in Blood Composition Slide 15 of 154 MPharm PHA112 The Circulatory System Constituents of Plasma WEEK 18 Component Albumins Examples Major protein constituent of plasma – total volume accounts for nearly 60% of all plasma proteins Antibodies; carriers of water-insoluble hormones, lipids, vitamins, etc Globulins Fibrinogen Essential to the coagulation process; fibrinogen is converted to fibrin, which forms the stable blood clot Other proteins Enzymes, coenzymes, hormones, etc Electrolytes Sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), chloride (Cl-), bicarbonate (HCO3-), and sulphate (SO4-) – needed for cell function Organic nutrients Lipids, cholesterol, carbohydrates, and amino acids provide energy for cellular activities in the body Organic waste products Urea, uric acid, creatinine, bilirubin and ammonium ions (NH4+) Slide 16 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 17 of 154 Constituents of Plasma MPharm PHA112 The Circulatory System Constituents of Plasma WEEK 18 Plasma Proteins Slide 18 of 154 MPharm PHA112 The Circulatory System WEEK 18 Formed or Cellular Elements Consist of 3 main cellular types red blood cells (erythrocytes) white blood cells (leukocytes) platelets (thrombocytes) Slide 19 of 154 MPharm PHA112 The Circulatory System WEEK 18 Formed or Cellular Elements Erythrocytes (red blood cells, RBCs) contain haemoglobin & transport O2 to cells Leukocytes (white blood cells, WBCs) mobile units of the body’s immune defence system transported in the blood to sites of injury or invasion by disease-causing microorganisms (pathogens) Platelets (thrombocytes) important in haemostasis, the arrest of bleeding from an injured blood vessel Slide 20 of 154 MPharm PHA112 The Circulatory System WEEK Erythrocytes (RBCs) 18 smooth, round & flexible biconcave discs Top view lack nuclei, mitochondria/most organelles 7.5 m contain large amounts of haemoglobin O2 & CO2 transport 2.0 m most abundant cell type Sectional view Males = 5.6-6.2 x 106/L Females = 4.2-5.4 x 106/L Infants = 5.0-6.5 x 106/L formation occurs in red bone marrow stimulated by erythropoietin (from kidney) Slide 21 of 154 MPharm PHA112 The Circulatory System Haemoglobin WEEK 18 iron-containing molecule that loosely & reversibly binds O2 synthesised & packed into RBCs during cell development an 22 tetrameric polypeptide-haem complex two each of & polypeptide chains (globin moiety) four iron-containing haem prosthetic groups each haemoglobin molecule can carry four O2 molecules also contributes to CO2 transport and pH buffering of blood Slide 22 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 23 of 154 The Haemoglobin Molecule MPharm PHA112 The Circulatory System WEEK 18 Slide 24 of 154 The Life & Times of RBCs MPharm PHA112 The Circulatory System WEEK Leukocytes (WBCs) 18 Two main cell categories distinguished microscopically Granulocytes (70%) Neutrophils (65%) Eosinophils (4%) Basophils (1%) Agranulocytes (30%) Lymphocytes (25%) Monocytes (5%) primarily function as defence agents defence against tumours, bacterial, viral & parasitic infections Slide 25 of 154 MPharm PHA112 The Circulatory System Granulocytes WEEK 18 Neutrophils multi-lobed nucleus (PMN) small purple granules in cytoplasm short life-span in circulation (6-8 h) “phagocytic specialists” first line of defence against invading microbial pathogens ingest or trap & destroy invading bacteria (pathogens) scavenge & clean up cellular debris act to slow & localize infection in active/acute bacterial infections Slide 26 of 154 MPharm PHA112 The Circulatory System Granulocytes WEEK 18 Eosinophils large, bi-lobed nucleus large red granules in cytoplasm phagocytic defend against parasitic infestations Attach to, and secrete substances to kill parasitic worms act to moderate allergic reactions in internal parasitic infestations & allergic conditions (e.g. asthma & hay fever) Slide 27 of 154 MPharm PHA112 The Circulatory System WEEK Granulocytes 18 Basophils deeply indented nucleus large, dark blue granules synthesise, store & release histamine & heparin major roles in hypersensitivity reactions infections Slide 28 of 154 MPharm PHA112 The Circulatory System Agranulocytes WEEK 18 Lymphocytes large, dark spherical nucleus thin rim of light blue cytoplasm major role in immune system in chronic infections 3 major cell types B cells – produce antibodies that target & mark invading bacteria & viruses for the ‘kill’ (humoral-mediated immunity) T cells – produce lymphokines that directly attack & kill invading virus and infected or tumour cells (cell-mediated immunity) Natural killer cells – attack & kill virus-infected and/or tumour cells Slide 29 of 154 MPharm PHA112 The Circulatory System Agranulocytes WEEK 18 Monocytes large, round /oval or kidney-shaped nucleus abundant agranular cytoplasm key role in immune system in acute infections phagocytic engulf & kill invading bacteria activate B and T cells scavenge dead pathogens & dust particles Slide 30 of 154 MPharm PHA112 The Circulatory System WEEK 18 Leukocytes Fight Against Microbial Infection Slide 31 of 154 MPharm PHA112 The Circulatory System Platelets (Thrombocytes) WEEK 18 granule-rich packages of cytoplasm key role in circulatory system maintain integrity of endothelial lining granules contain serotonin (5-HT), Ca2+, enzymes, ADP & platelet-derived growth factor (PDGF) initiate haemostasis - the arrest of bleeding short life span – ~7-10 days Slide 32 of 154 MPharm PHA112 The Circulatory System WEEK Platelets & Haemostasis 18 vascular injury exposes collagen & basement membrane proteins platelet adhesion, activation & aggregation activated/aggregated platelets release pro-aggregatory mediators – ADP & thromboxane A2 activated platelets help trigger thrombin generation initiation of the coagulation cascade mesh-like fibrin deposition clot stabilisation Slide 33 of 154 MPharm PHA112 The Circulatory System WEEK 18 Formed or Cellular Elements Summary Slides Slide 34 of 154 MPharm PHA112 The Circulatory System WEEK 18 Formed or Cellular Elements Summary Slides Slide 35 of 154 MPharm PHA112 The Circulatory System WEEK 18 Formed or Cellular Elements of Blood & their Functions Slide 36 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 37 of 154 Blood Cell Production (Haematopoiesis) MPharm PHA112 The Circulatory System WEEK WEEK 26 18 MPharm Programme Normal Systems The Circulatory System 2 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Circulatory System WEEK 18 The Heart Slide 39 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 40 of 154 The Heart MPharm PHA112 The Circulatory System Gross Anatomy of the Heart WEEK 18 A hollow, muscular organ – about the size of a clenched fist Located in the mediastinum, a section of the thoracic cavity midline between the sternum (breastbone) & the vertebrae (backbone) Surrounded by a double-layered membrane – the pericardium inner, visceral pericardium – covers the entire heart (epicardium) outer, parietal pericardium – attaches to the great vessels, sternum & diaphragm pericardial cavity – contains 30-50 ml serous fluid Slide 41 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 42 of 154 Location of the Heart MPharm PHA112 The Circulatory System WEEK The Heart as a Pump 18 a 4-chambered muscular organ functions as two separate functional pumps left- & right-sided pumps each pump is divided into an upper chamber (atrium) & a lower chamber (ventricle) each upper chamber opens into the lower chamber through a valve (tricuspid or mitral) left & right pumps separated by a continuous muscular partition (septum) Slide 43 of 154 MPharm PHA112 The Circulatory System The Heart WEEK 18 Slide 44 of 154 MPharm PHA112 The Circulatory System WEEK The Heart as a Pump 18 The Right-sided Pump concerned with pulmonary circulation & gaseous exchange receives de-oxygenated blood from the systemic circulation pumps it to the lungs (pulmonary circulation) for reoxygenation & CO2 removal lower chamber (ventricle) opens into pulmonary artery via pulmonic valve Slide 45 of 154 MPharm PHA112 The Circulatory System WEEK The Heart as a Pump 18 The Left-sided Pump concerned with systemic circulation and O2 & nutrient supply receives re-oxygenated blood from the lungs (pulmonary circulation) pumps it into the systemic circulation for O2 and nutrient supply to organs & tissues lower chamber (ventricle) opens into aorta via aortic valve Slide 46 of 154 MPharm PHA112 The Circulatory System The Heart WEEK 18 Slide 47 of 154 MPharm PHA112 The Circulatory System WEEK 18 Dual Pump Action of the Heart Slide 48 of 154 MPharm PHA112 The Circulatory System WEEK 18 Circulation Patterns of the Heart Slide 49 of 154 MPharm PHA112 The Circulatory System WEEK Blood Vessels of the Heart 18 Two main types The Great Cardiac Vessels Carry blood to & from the heart chambers and systemic & pulmonary circulations Include: Superior & inferior vena cavae Pulmonary artery Pulmonary veins Aorta Slide 50 of 154 MPharm PHA112 The Circulatory System WEEK Blood Vessels of the Heart 18 Two main types The Coronary Vessels form the Coronary Circulation – specialised blood supply system of the heart Include: Left & right coronary arteries Coronary sinus, Great/Middle/Anterior & Posterior cardiac veins, Thebesian veins, etc Slide 51 of 154 MPharm PHA112 The Circulatory System WEEK Blood Vessels of the Heart 18 Aorta – accepts output of the left ventricle; first vessel of the systemic circulation; sustains highest systolic pressure ~140 mmHg Pulmonary artery – accepts output of the right ventricle; first vessel of the pulmonary circulation; sustains peak pressure ~25 mmHg Superior vena cava / inferior vena cava – largest vessels returning deoxygenated blood to heart (right atrium) from systemic circulation Pulmonary veins – largest vessels returning oxygenated blood to heart (left atrium) from pulmonary circulation Coronary arteries & veins – supply blood to cardiac muscle tissue; branch off from the aorta immediately above aortic valve; veins drain blood into right atrium Slide 52 of 154 MPharm PHA112 The Circulatory System WEEK 18 The Vessels of the Heart Anterior View Slide 53 of 154 MPharm PHA112 The Circulatory System WEEK 18 The Vessels of the Heart Posterior View Slide 54 of 154 MPharm PHA112 The Circulatory System WEEK Coronary Circulation 18 Myocardial O2 & nutrient demand heart beats constantly through life requires constant & adequate supply of O2 & nutrients Myocardial O2 & nutrient supply supplied by special network of blood vessels consists of left & right coronary arteries Delicate balance between demand & supply reduced coronary blood flow during systole disproportionate share of cardiac output high O2 extraction low O2 reserve Slide 55 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 56 of 154 The Coronary Vessels MPharm PHA112 The Circulatory System WEEK 18 Slide 57 of 154 The Coronary Vessels MPharm PHA112 The Circulatory System The Heart Valves WEEK 18 4 strategically placed valves one-way opening prevents backflow of blood ensure unidirectional flow of blood through the heart AV valves (Right & Left) Tricuspid valve – between right atrium & ventricle Bicuspid / Mitral valve – between left atrium & ventricle Semilunar valves Pulmonic valve – between right ventricle & pulmonary artery Aortic valve – between left ventricle & aorta Slide 58 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 59 of 154 The Heart Valves MPharm PHA112 The Circulatory System WEEK 18 Slide 60 of 154 The Heart Valves MPharm PHA112 The Circulatory System WEEK 18 Slide 61 of 154 The AV Heart Valves MPharm PHA112 The Circulatory System WEEK 18 The Semilunar Heart Valves Slide 62 of 154 MPharm PHA112 The Circulatory System WEEK The Heart Wall 18 Consists of three distinct layers Endocardium innermost thin lining of endothelial cells permits smooth flow of blood & prevents clotting Myocardium middle layer – composed of cardiac muscle forms the bulk of the heart wall Epicardium protective, outer layer of the heart wall embeds coronary blood vessels Slide 63 of 154 MPharm PHA112 The Circulatory System WEEK 18 Slide 64 of 154 Layers of the Heart Wall MPharm PHA112 The Circulatory System Cardiac Cell Types WEEK 18 Two main specialised types of heart cells Contractile cells Cardiac muscle cells – 99% of heart cells Largely constitute the myocardium & septum Mediate mechanical, pumping work of the heart Form interlacing bundles – arranged spirally around circumference of the heart Electrically quiescent – do not normally initiate their own action potentials Comprise: Atrial & ventricular muscle cells Slide 65 of 154 MPharm PHA112 The Circulatory System WEEK Cardiac Cell Types 18 Two main specialised types of heart cells Electrical or Autorhythmic cells Do not contract Specialized for initiating & conducting action potentials activation & contraction of muscle cells Include: Sinoatrial node (SA node) Atrioventricular node (AV node) Bundle of His (Atrioventricular bundle) Purkinje fibres Slide 66 of 154 MPharm PHA112 The Circulatory System WEEK 18 General Properties of Cardiac Cells The Cardiac Resting Membrane Potential cell membrane at rest is polarized – inside is negative compared to outside physico-chemical basis unequal distribution of ions across cell membrane ions can only cross the cell membrane via ion channels opening & closing of ion channels is voltage & timedependent K+ channels selectively open in the cell membrane at rest RMP is closer to K+ equilibrium potential slow spontaneous depolarisation in automatic cells Slide 67 of 154 MPharm PHA112 The Circulatory System WEEK 18 General Properties of Cardiac Cells Excitability ability of cardiac cells to respond to electrical stimulus by firing an action potential (AP) AP due to voltage- & time-dependent opening & closing of specific ion channels 2 types of cardiac APs – fast & slow conduction characteristics fast AP – high conduction velocity, ~1-4 ms/s slow AP – slow conduction velocity, ~0.02-0.1 ms/s more easily blocked liable to conduction failure at high repetition rates Slide 68 of 154 MPharm PHA112 The Circulatory System WEEK 18 Types of Cardiac Action Potentials Fast AP (e.g. Ventricular Muscle Cell) Slow AP (e.g. SA nodal cell) Slide 69 of 154 MPharm PHA112 The Circulatory System WEEK 18 Types of Cardiac Action Potentials Underlying Ion Channel Activity Fast AP Slide 70 of 154 MPharm Slow AP PHA112 The Circulatory System WEEK 18 Cardiac Cell Types & Characteristic APs Slide 71 of 154 MPharm PHA112 The Circulatory System
