IP1000 Introduction to Pathophysiology Cardiovascular Disease 1 PDF

Introduction to Pathophysiology IP1000 Introduction to Pathophysiology Heart of the Matter: Cardiovascular Disease 1 Dr Elsamaul Elhebir...

Introduction to Pathophysiology IP1000 Introduction to Pathophysiology Heart of the Matter: Cardiovascular Disease 1 Dr Elsamaul Elhebir Acknowledgement: A/Prof Lisa Tee Cardiovascular Pathophysiology I  “We acknowledge the Traditional Owners of this Land, the Nyungar people, and pay respect to the Elders of their community.” Cardiovascular Pathophysiology I  Commonwealth of Australia Copyright Regulations 1969 WARNING This material has been copied and communicated to you by or on behalf of Curtin University of Technology pursuant to Part Vb of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any further copying or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice Cardiovascular Pathophysiology I  Your program map for Introduction to Pathophysiology Week 1 Week 2 Week 3 Week 4 MODULE 1a MODULE 1b MODULE 2 MODULE 3 Understanding Disease: How Cell injury and ANS: Inflammation Underpinning Arthritis do we respond? Disease & Health Week 8 Week 5 & 6 MODULE 5 MODULE 4 Week 7 COPD & Diabetes Study Free Pulmonary Pathophysiology Week 9 & 10 Week 11 & 12 Week 13 MODULE 6 MODULE 7 MODULE 8 Renal Cardiovascular Gastrointestinal pathophysiology Pathophysiology Pathophysiology Cardiovascular Pathophysiology I  Cardiovascular pathophysiology Introduce CASE: Meet Mr Hartman - Heart Failure Review normal function of the cardiovascular system Concepts of ECG and action potential in cardiac tissue Alterations of cardiovascular function Some cardiovascular disorders: Hypertension, atherosclerosis, ischaemia heart disease, myocardial infarction, stroke, heart failure, arrhythmias. Recommended Reading: Huether SE and McCance KL (Eds.). Understanding Pathophysiology. St Louis: Elsevier, 5th Edition (2012) Chapter pp. 594-597; 6th edition (2017) chapter 23 and 24 pp 569-637; 7th Edition (2020) Chapter 25 and 26 pp 563-638, Chapter 22 pp 496-499; Chapter 17 pp 395-399 (stroke) Week week11 12&&12 13 Cardiovascular Pathophysiology More in Year 3 Semester 1 Cardiovascular Pathophysiology I  Learning Outcomes Part a: Outline the normal electrophysiology of the heart Identify and explain the factors that affect cardiac output Part b: Rationalise how blood pressure is regulated Describe the causes, risk factors & pathophysiology of hypertension Part c: Describe the causes, risk factors & pathophysiology of atherosclerosis Cardiovascular Pathophysiology I  Module Outline 1. Meet Mr Hartman 2. 7. Case study Normal cardiac Heart Failure function Arrhythmias Cardiac Output 6. Module Ischaemic Heart Disease 3. Cardiovascular Regulation of Angina Pathophysiology BP & Myocardial Infarction Stroke Hypertension 5. 4. Haemostasis Arteriosclerosis Platelet aggregation Atherosclerosis Blood clotting Thrombosis Cardiovascular Pathophysiology I  Meet Mr. Hartman Age 55, overweight executive Ex-smoker and social drinker Mr Hartman presents with shortness of breath Complains of fatigue after a steady 10 minutes walk Chest congestion Swelling of ankle Cardiovascular Pathophysiology I  Mr. Hartman…..PMHx Mr Hartman’s medical history (PMHx) Hypertension (HTN) Elevated cholesterol Ischaemic Heart Disease Myocardial Infarction (Heart attack) x2 Stroke Heart Failure (HF) Atrial Fibrillation (AF) Cardiovascular Pathophysiology I  Mr. Hartman…..Assessment https://classconnection.s3.amaz onaws.com/874/flashcards/260 BP – 160/100 mmHg 8874/jpg/pitting_edema136158 1056399.jpg Pulse (HR) – 100 bpm Respiratory rate (RR) – 28/min (normal 12-18 BPM) Pitting oedema of the extremities Echocardiogram: Ejection Fraction 20-25% (Normal 70%) ECG: http://1.bp.blogspot.com/-vCwKlWlqJ-c/U9_zveGBmEI/AAAAAAAAbAo/FQMV3XJ3kvw/s1600/Atrial+fibrillation+with+RVR+02.png Cardiovascular Pathophysiology I  Mr. Hartman… Treatment For Mr Hartman’s HF: ACE inhibitors and Beta Blockers Cardiac glycosides Diuretics Cardiovascular Pathophysiology I  Introduction to Pathophysiology IP1000 Introduction to Pathophysiology Heart of the Matter: Cardiovascular Disease 1 Part a: Normal ECG and Key Terms Cardiovascular Pathophysiology I  Learning Outcomes Part a: Outline the normal electrophysiology of the heart Identify and explain the factors that affect cardiac output Part b: Rationalise how blood pressure is regulated Describe the causes, risk factors & pathophysiology of hypertension Part c: Describe the causes, risk factors & pathophysiology of atherosclerosis Cardiovascular Pathophysiology I  Anatomy – Review Structure & Function HSF revisited….. Atria Ventricles Pericardium Myocardium Endocardium Heart valves – pulmonary, mitral, aortic, tricuspid Myocardial muscle http://www.texasheart.org/hic/anatomy/anatomy2.cfm Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 7th Edition (2020), Mosby Elsevier, Fig 25.2B, pp 565 Cardiovascular Pathophysiology I  Cardiac Cycle Cardiac Cycle: Sequential contraction & the relaxation of atria and ventricles During diastole, blood fills the ventricles During systole, blood is propelled out of the ventricles Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.5, pp 554; 7th Edition (2020) Fig 25.3 pp566. Cardiovascular Pathophysiology I  Cardiac Cycle AV valves open Cardiac Cycle: 1. Atrial systole, blood pump into ventricles from atrium 2. Isovolumetric ventricular contraction. AV valves open Ventricular volume remains constant 3. Ejection. RV ejects deoxygenated blood into lungs and LV ejects oxygenated blood to systemic circulation. 4. Isovolumetric ventricular relaxation. Both sets of valves are closed. Semilunar Ventricles relax. valves open 5. Passive ventricular filling. AV valve are forced open, blood rushes into the Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.7, pp 555; 7th Edition (2020) Fig 25.4, pp 567 relaxing ventricles. Cardiovascular Pathophysiology I  Heart: Normal Electrophysiology 1 2 hCa2+ 0 mV 0 hNa+ 3 iK+ 4 4 4 -85 mV Phases of Action Potential 0 Depolarisation 1 Early rapid repolarisation Two types of cardiac tissue Ordinary cardiac muscle 2 Plateau Specialised conducting tissue 3 Repolarisation 4 Diastolic depolarisation Cardiovascular Pathophysiology I  Factors Affecting Cardiac Action Potential 1 2 hCa2+ 0 mV 0 hNa+ 3 iK+ 4 4 4 -85 mV Effective Refractory Period (ERP) Phase 0: Changes on Na+ influx affect intensity of the action potential Phase 2: Plateau phase associated with prolonged increase in Ca2+ ERP: Changes in K concentration affect duration of the action potential permeability of muscle cell membrane Cardiovascular Pathophysiology I  Electrocardiogram (ECG) ECG = Recording of the electrical activity of the heart Electrodes attached to the surface of the body → detect electrical changes in myocardial cells Contraction of any myocyte → electrical changes called depolarisation Use of ECG: To detect electrical disturbances & abnormalities in heart rhythm Cardiovascular Pathophysiology I  Action Potential – ECG Relationship Pharmacology, Brenner GM, Stevens CW, 2nd Edn, 2006, Brenner Fig 14.1 Cardiovascular Pathophysiology I  Electrocardiogram (ECG) P-wave: Atrial depolarisation QRS complex: Ventricular depolarisation T-wave: Ventricular repolarisation Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.10, pp 559 Cardiovascular Pathophysiology I  Heart: Normal Electrophysiology R 2 T 1 3 P QS SA node aatrium a AV node a purkinje fibre aventricles Atrial depolarisationaventricular depolarisationaventricular repolarisation 1 2 3 Cardiovascular Pathophysiology I  Pre-tutorial questions: 1. Outline the blood flow from the heart to the lungs. 2. Outline the blood flow from the heart to the body and back to the heart. 3. Describe the phases of the cardiac cycle. Cardiovascular Pathophysiology I  Key Cardiovascular Terms Preload Frank Starling Mechanism Afterload Myocardial Contractility (Inotropy) Ejection Fraction (EF) Stroke Volume (SV) Heart Rate (HR) Cardiac Output (CO) Cardiovascular Pathophysiology I  Preload From systemic From lung via Volume & pressure generated in the circulation via pulmonary vena cavae veins ventricle at the end of diastole Ventricular end-diastolic volume (VEDV) Preload determined by 2 factors: Venous return during diastole End-systolic volume Causes lengthening of the myocardial fibres = ventricular stretch Ventricular stretch Frank-Starling mechanism Cardiovascular Pathophysiology I  Frank-Starling Mechanism ‘The ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return’ Length-tension relationship of preload to myocardial contractility Ventricular stretch Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, pp Fig 22.16, 564; 7th Edition (2020) Fig 25.14, pp 575 Cardiovascular Pathophysiology I  Afterload Vasoconstriction The force needed to be generated → increase resistance to eject blood from the heart →increase afterload → Decrease SV Varies depending on systemic vascular resistance and ventricular wall tension Increase vascular resistance → increase afterload → decrease SV → increase end systolic volume To lung via To systemic pulmonary circulation via artery aorta Cardiovascular Pathophysiology I  Myocardial Contractility Inotropy → force of contraction Interaction between actin and myosin filaments during cardiac muscle contraction Needs energy from ATP, Ca, Na & K Relates to Frank Starling mechanism Porth’s Pathophysiology. Concepts of Altered Health States, 9th Edition, pp 722 Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 7th Edition (2020) , Mosby Elsevier, Fig 25.11, pp 573 Cardiovascular Pathophysiology I  Myocardial Contractility 1 Influx of Ca2+ 1. 2 Triggers Ca2+ release from 2. 5 scarcoplasmic reticulum 1 2 (SR) 3 Ca2+ binds to troponin C → 3. 3 contraction of myofibrils 4 (systole) 4 Reuptake of Ca2+ into SR 4. and 5 Ca2+ efflux of by Na+ / Ca2+ 5. exchange transporter→ relaxation (diastole) Image from: Porth’s Pathophysiology. Concepts of Altered Health States, 9th Edition, Fig 43.1, pp 869 Cardiovascular Pathophysiology I  Effect of Cardiac Contractility on Cardiac output Increase contractility → Increase CO CO= The volume of blood pumped out of the heart per minute CO = SV x HR CO is changed by alterations in SV or HR Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.7, pp 565; 7th Edition (2020) Fig 25.13, pp 575 Cardiovascular Pathophysiology I  Factors enhancing cardiac output Image from: Marieb Human Anatomy and Physiology, 9th Edition, pp 705 Cardiovascular Pathophysiology I  Summary of key terms Preload End diastolic volume Blood from pulmonary veins and venae cavae fill the ventricles Stroke Volume (SV) Amount of blood expelled during contraction (systole) Afterload Afterload When ventricles contract the blood is expelled into the arteries and if anything impedes it, SV will decrease and the work effort will increase. Ejection Fraction (EF) % of blood pumped out of the ventricle with each contraction Cardiac Output (CO) Volume of blood pumped out of heart per min Preload Cardiovascular Pathophysiology I  Pre-tutorial questions: 4. Define preload and afterload. 5. Describe factors which enhance cardiac output Cardiovascular Pathophysiology I  What is the impact of Mr Hartman’s HYPERTENSION have on the following which leads to Heart Failure Afterload Preload CO Cardiovascular Pathophysiology I  Introduction to Pathophysiology IP1000 Introduction to Pathophysiology Heart of the Matter: Cardiovascular Disease 1 Part b: Regulation of BP and Hypertension Cardiovascular Pathophysiology I  Learning Outcomes Part a: Outline the normal electrophysiology of the heart Identify and explain the factors that affect cardiac output Part b: Rationalise how blood pressure is regulated Describe the causes, risk factors & pathophysiology of hypertension Part c: Describe the causes, risk factors & pathophysiology of atherosclerosis Cardiovascular Pathophysiology I  Arterial Pressure Arterial BP = CO x Total Peripheral Resistance Systolic BP = pressure during ventricular contraction Diastolic BP = pressure during ventricular filling / relaxation Arterial pressure is regulated to maintain total plasma volume (TPV) and tissue perfusion Cardiovascular Pathophysiology I  Factors Influencing Blood Pressure SNS / PNS (neural) Arterial BP = CO x TPR HR → Cardiac output CO = Cardiac Output Peripheral resistance TPR = Total Peripheral Resistance vasoconstriction / vasodilation Fluid volume →Hormones Renin-angiotensin-Aldosterone Arterial pressure is regulated to ADH maintain total plasma volume (TPV) Natriuretic Peptides Cardiovascular Pathophysiology I  Hormonal regulation of total plasma volume ADH (antidiuretic hormone) Aldosterone Increase water retention → increase total plasma volume (TPV) NPs (natriuretic peptides) Promote water and sodium loss → decrease TPV Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.32, pp 576; 7th Edition (2020) Fig 25.24 pp 585 Cardiovascular Pathophysiology I  Effects of Cardiac Output on BP Increased CO →increases arterial blood volume → arterial pressure Decreased CO →will cause a drop in pressure Factors which affect CO will also affect BP – Neural (SNS / PNS) – Hormonal Remember: BP = CO x TPR Remember: CO = SV x HR Cardiovascular Pathophysiology I  Effect of Peripheral Resistance on BP Determined by changes in diameter of the arterioles Vasoconstriction increases pressure Vasodilatation decreases pressure Control of Peripheral Resistance Neural control (SNS) - via Baroreceptors Hormonal control –RAAS –ADH Cardiovascular Pathophysiology I  SNS Neural Regulation of Blood Pressure Sympathetic nervous system mediated control: 1 Arterioles 2 Postcapillary Venules 3 Heart 4 Kidney Renin-Angiotensin- Aldosterone system - Baroreceptors ……From Module 2: ANS Cardiovascular Pathophysiology I Cardiovascular drugs/Dr Lisa Tee/Curtin  Sympathetic Control of BP In response to a drop in BP Via baroreceptors 1 2 1 Alpha 1 stimulation in blood vessels - vasoconstriction 2 Beta 1 stimulation in heart hHR and contractility c hCO 1 3 Beta 1 stimulation in kidney release of renin c vasoconstriction and hCO 3 BP = CO x TPR Net result c BP rises Cardiovascular Pathophysiology I  Hormonal Regulation of BP Renin-angiotensin-aldosterone system (RAAS) Release of renin stimulated by drop in BP Renin is secreted by the kidney Net result → formation of Angiotensin II Angiotensin II (AGII) = Powerful vasoconstrictor AGII stimulates release of aldosterone Also triggers release of ADH from posterior pituitary ADH (Vasopressin) Causes reabsorption of water by the kidney Revisit Renal Module Increases blood plasma volume Also a POTENT vasoconstrictor Cardiovascular Pathophysiology I  Renin- Angiotensin- Aldosterone System In response to a drop in BP Release of Renin 1 2 Conversion of angiotensinogen to Angiotensin I (AI) 4 5 3 Conversion of AI to AII 3 4 AII is a powerful vasoconstrictor and stimulates release of 2 aldosterone 1 5 Aldosterone causes salt retention Net result c BP rises Picture from: http://www.google.com.au/imgres?q=regulation+of+blood+pressure+renin+angiotensin+system&um=1&hl=en&biw=1680&bih=869&tbm=isch&tbnid=dgrvk4SctbCptM:&imgrefurl=http://www.merckmanuals.com/home/heart _and_blood_vessel_disorders/high_blood_pressure/high_blood_pressure.html&docid=2i9fnX4qsjBIqM&imgurl=http://www.merckmanuals.com/media/home/figures/CVS_regulating_blood_pressure_renin.gif&w=347&h=323 &ei=5r0DUJ2HIcujiAfRibn8Bw&zoom=1&iact=hc&vpx=324&vpy=149&dur=46&hovh=217&hovw=233&tx=138&ty=97&sig=115295167741062497607&page=1&tbnh=161&tbnw=173&start=0&ndsp=33&ved=1t:429,r:1,s:0,i:73) Cardiovascular Pathophysiology I  Renin- Angiotensin- Aldosterone System Renin 1 Is secreted from juxta- glomerular apparatus in kidney 4 Angiotensinogen 2 3 Is secreted from liver ACE 3 2 Is secreted from the lungs ADH 4 1 Is secreted from posterior pituitary gland Image from: Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, pp 577 Cardiovascular Pathophysiology I  Summary: Factors Regulating BP Will be revisited in Year 3 Sem 1 Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 22.30, pp574.; 7th Edition (2020) Fig 25.22 pp583 Cardiovascular Pathophysiology I  Reflect and review: Describe the role of the renin-angiotensin system in the regulation of blood pressure. Cardiovascular Pathophysiology I  Mr. Hartman…..PMHx Mr Hartman’s medical history (PMHx) Hypertension (HTN) Elevated cholesterol Ischaemic Heart Disease Myocardial Infarction (Heart attack) x2 Stroke Heart Failure (HF) Atrial Fibrillation (AF) Cardiovascular Pathophysiology I  Hypertension A sustained elevation of systemic arterial blood pressure (BP). Results from a sustained increase in peripheral resistance, increase in blood volume or both. Systolic BP > 140 mmHg Diastolic BP > 90 mmHg http://www.blogsmonitor.com/news/gallery/hypertension/hypertension.jpg Cardiovascular Pathophysiology I  Stages of Hypertension https://www.heartfoundation.org.au/conditions/hypertension https://www.heartfoundation.org.au/getmedia/c83511ab-835a-4fcf-96f5-88d770582ddc/PRO-167_Hypertension-guideline-2016_WEB.pdf Cardiovascular Pathophysiology I  Primary vs Secondary Hypertension Primary HTN (essential / idiopathic) Elevated BP with unknown cause Most common → 90-95% of all cases Combination of systolic and diastolic HTN Secondary HTN Elevated BP with known, specific cause Less common → 5-10% of all cases Caused by an underlying disease, eg renal disease Cardiovascular Pathophysiology I  Hypertension: Risk Factors Primary HTN Secondary HTN Age (>55 for men, >65 for women) Contributing factors: Excessive alcohol intake Coarctation of aorta Cigarette smoking Renal disease Diabetes Mellitus Endocrine disorders (eg Excess sodium intake phaechromocytoma, thyroid Gender disorders) Elevated serum lipids Neurological disorders Family history Obesity (BMI > 30) Ethnicity Sedentary lifestyle Socioeconomic status Stress http://www.mayoclinic.org/diseases-conditions/coarctation-of-the-aorta/multimedia/coarctation-of-the-aorta/img-20007864 https://www.dreamstime.com/stock-illustration-pheochromocytoma-kidneys-adrenal-glands-labeled-diagram-image42672677 Cardiovascular Pathophysiology I  Pathophysiology of Hypertension FIGURE 26.4 Pathophysiology of Hypertension. Numerous genetic vulnerabilities have been linked to hypertension and these, in combination with environmental risks, cause neurohumoral dysfunction (sympathetic nervous system [SNS], renin- angiotensin-aldosterone [RAA] system, natriuretic hormones) and promote inflammation and insulin resistance. Insulin resistance and neurohumoral dysfunction contribute to sustained systemic vasoconstriction and increased peripheral vascular resistance. Inflammation contributes to renal dysfunction, which, in combination with the neurohumoral alterations, results in renal salt and water retention and increased blood volume. Increased peripheral vascular resistance and increased blood volume are two primary causes of sustained hypertension. Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9, pp 589; 7th Edition (2020) Fig 26.4 pp595 Cardiovascular Pathophysiology I  Complications of Hypertension HTN → stiffness in the arteries Kidney Heart Chronic kidney disease (CKD) Left ventricular hypertrophy (LVH) Angina Eyes (Retina) Myocardial infarction (MI) Hypertensive Heart failure (HF) retinopathy Blindness Brain http://www.mrcpstudy.com/hypertensive-retinopathy/ Stroke Peripheral Vascular Transient ischaemic attack (TIA) Peripheral arterial disease (PAD) http://www.youtube.com/watch?v=tAmL bclSucQ&feature=youtube_gdata_player http://www.123rf.com/stock-photo/brain_stroke.html?mediapopup=39163375 Cardiovascular Pathophysiology I  Introduction to Pathophysiology IP1000 Introduction to Pathophysiology Heart of the Matter: Cardiovascular Disease 1 Part c: Arteriosclerosis and Atherosclerosis Cardiovascular Pathophysiology I  Learning Outcomes Part a: Outline the normal electrophysiology of the heart Identify and explain the factors that affect cardiac output Part b: Rationalise how blood pressure is regulated Describe the causes, risk factors & pathophysiology of hypertension Part c: Describe the causes, risk factors & pathophysiology of atherosclerosis Cardiovascular Pathophysiology I  Mr. Hartman…..PMHx Mr Hartman’s medical history (PMHx) Hypertension (HTN) → hardening of arteries → arteriosclerosis Elevated cholesterol → Atherosclerosis Ischaemic Heart Disease Myocardial Infarction (Heart attack) x2 Stroke Heart Failure (HF) Atrial Fibrillation (AF) Cardiovascular Pathophysiology I  ARTERIOSCLEROSIS Vessels made up of 3 layers: Site of injury leading to Tunica intima (endothelial cells) inflammation→ thickening and Tunica media hardening of arteries Adventitia Arteriosclerosis is a chronic disease of the arterial system characterised by abnormal thickening & hardening of wall of vessels Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.7, pp 594 Cardiovascular Pathophysiology I  Arteriosclerosis vs Atherosclerosis ARTeriosclerosis is general term describing the hardening of medium and large arteries ATHerosclerosis is a specific kind of arteriosclerosis → the pathological build up of fatty lesion Can affect vessels which supply of blood to important areas: Heart Brain Atherosclerosis → affects endothelial Kidney cells in tunica intima → inflammation → formation of fatty atheroma plaque Lungs → occlusion of blood flow Liver → Ischaemic Heart Disease → Myocardial Infarction Limbs Image from: Porth’s Pathophysiology. Concepts of Altered Health States, 9th Edition, Fig 30.7, pp 747 Cardiovascular Pathophysiology I  1 Atherosclerosis Injurious environment: Hypertension Smoking Increased LDL & 2 decreased HDL cholesterol 1. Endothelial cell injury (in tunica intima) Elevated C-reactive Atherosclerosis begins with injury to endothelial protein cells (ECs) Increased serum Injured ECs become inflamed fibrinogen Inflamed ECs CANNOT make normal amount Diabetes antithrombic agents and vasodilating of cytokines Insulin resistance 2. Adhesion to Endothelium Oxidative stress Macrophages adhere to injured EC lining Infection And release inflammatory cytokines (eg TNF- Periodontal disease alpha, C-reactive protein) Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9pp 596; 7th Edition (2020) Fig 26.7 Cardiovascular Pathophysiology I  Atherosclerosis 4 3 3. Foam cells Further recruitment of monocytes which differentiate into macrophages Lipids accumulated in the vessel intima. Macrophages penetrate intima and engulf lipids Macrophages filled with lipids are called FOAM CELLS 4. Fatty Streak Accumulation of foam cells form a lesion called FATTY STREAK Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9pp 596; 7th Edition (2020) Fig 26.7 Cardiovascular Pathophysiology I  Atherosclerosis 5 5. Fibrous Plaque Macrophages also release growth factors → increase proliferation of smooth muscle cells (SMCs) SMCs migrate to intima SMCs in intima produce collagen and migrate over the fatty streak forming a FIBROUS PLAQUE Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9pp 596; 7th Edition (2020) Fig 26.7 Cardiovascular Pathophysiology I  Atherosclerosis 7 Platelet adhesion 6 Platelet adhesion 6. Complicated lesion The fibrous plaque → calcify →protrude into the vessel lumen →obstruct blood flow to distal tissues (especially during exercise), which may cause symptoms (e.g., angina) Plaque that has ruptured is called complicated plaque 7. Thrombus Once plaque ruptures → initiates platelet adhesion and activate clotting cascade leading to THROMBUS formation. Thrombus may suddenly occlude vessels → myocardial ischaemia → infarction Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9pp 596; 7th Edition (2020) Fig 26.7 Cardiovascular Pathophysiology I  Atherosclerosis Anti-thrombotics  Vasodilation 1. Injury to 1. Inflammation ENDOTHELIUM 2. MACROPHAGE adhere to endothelium and release cytokines which further injure endothelium 3. Macrophages engulf lipids forming FOAM CELLS 4. Accumulation of foam cells form FATTY STREAK 5. Macrophages release growth factor results in proliferation of smooth muscle cells → → → FIBROUS PLAQUE 6.COMPLICATED PLAQUE 7. THROMBUS Understanding pathophysiology. Heuther, McCance, Brash and Rote. 5th Edition, Mosby Elsevier, Fig 23.9pp 596; 7th Edition (2020) Fig 26.7 Cardiovascular Pathophysiology I  Understanding pathophysiology. Heuther, McCance, Brash, Mosby Elsevier, 7th Edition (2020) Fig 26.8 Cardiovascular Pathophysiology I  FIGURE 24-8 Low-Density Lipoprotein Oxidation. (1) Low-density lipoprotein (LDL) enters the arterial intima through an intact endothelium. In hypercholesterolemia, the influx of LDL exceeds the eliminating capacity and an extracellular pool of LDL is formed. This is enhanced by association of LDL with the extracellular matrix. (2) Intimal LDL is oxidized through the action of oxygen free radicals formed by enzymatic or nonenzymatic reactions. (3) This generates proinflammatory lipids that induce endothelial expression of the adhesion molecule; vascular cell adhesion molecule-1 activates complement and stimulates chemokine secretion. All of these factors cause adhesion and entry of mononuclear leukocytes, particularly monocytes and T lymphocytes. (4) Monocytes differentiate into macrophages. Macrophages up-regulate and internalize oxidized LDL and transform into foam cells. Macrophage update of oxidized LDL also leads to presentation of its fragments to antigen-specific T cells. (5) This induces an autoimmune reaction that leads to production of proinflammatory cytokines. Such cytokines include interferon-gamma, tumor necrosis factor-alpha, and interleukin-1, which act on endothelial cells to stimulate expression of adhesion molecules and procoagulant activity; on macrophages to activate proteases, endocytosis, nitric oxide (NO), and cytokines; and on smooth muscle cells (SMCs) to induce NO production and inhibit growth, collagen, and actin expression. (Modified from Crawford MH et al: Cardiology, ed 3, London, 2010, Mosby.) Understanding pathophysiology. Heuther, McCance, Brash, Mosby Elsevier, 7th Edition (2020) Fig 26.8 Cardiovascular Pathophysiology I  Atherosclerosis affects the coronary arteries Any vascular disorder that narrows or occludes the coronary arteries →Atherosclerosis is main cause Reduced blood supply to the heart leads to: IHD (Ischaemic heart disease) = CAD (Coronary artery disease) https://d15mj6e6qmt1na.cloudfront.net/files/images/0190/9958/1-1- 11_Atherosclerosis.jpg Cardiovascular Pathophysiology I  Mr. Hartman…..PMHx Mr Hartman’s medical history (PMHx) Hypertension (HTN) → hardening of arteries →arteriosclerosis Elevated cholesterol → Atherosclerosis Ischaemic Heart Disease →Angina Myocardial Infarction (Heart attack) x2 Stroke Heart Failure (HF) To be continued in CVD Atrial Fibrillation (AF) Part 2 Cardiovascular Pathophysiology I  Reflect and review: Explain the relationship between atherosclerosis and angina. In your answer describe the sequential stages of atherosclerosis and explain how atherosclerosis can manifest into angina See tutorial case study – Mr JD Cardiovascular Pathophysiology I  Case Scenario Mr JD is a 65-year old man. He is overweight, has a history of hypertension, high LDL-cholesterol levels and is a smoker. He has been admitted to hospital with a history of chest pain that developed with minimal exertion. Blood tests and ECG analysis demonstrate no myocardial infarction. The doctor told him he had ‘hardening of the arteries’ and that he now has angina. This patient has a history of hypertension. Hypertension is known to increase the risk of CVD atherosclerotic cardiovascular disease including angina. Tute 1 1. With regard to cardiovascular function, explain the effect of hypertension on afterload and the secondary effect this has on preload. 2. How does this affect cardiac output and what might this mean for someone experiencing angina associated with exercise? 3. Briefly explain (using correct terminology), what the doctor meant by ‘hardening of the arteries’. 4. Describe the development of atherosclerosis. Cardiovascular Pathophysiology I  Case Scenario Mr JD is a 65-year old man. He is overweight, has a history of hypertension, high LDL-cholesterol levels and is a smoker. He has been admitted to hospital with a history of chest pain that developed with minimal exertion. Blood tests and ECG analysis demonstrate no myocardial infarction. The doctor told him he had ‘hardening of the arteries’ and that he now has angina. This patient has a history of hypertension. Hypertension is known to increase the risk of CVD atherosclerotic cardiovascular disease including angina. Tute 2 5. Describe angina and how it occurs. Also describe the likely consequences of Mr JD’s condition. 6. Cardiovascular infarction with thrombosis relates to the stability of the fibrous cap over an atherosclerotic plaque. Explain why rupture, ulceration or erosion of a plaque may lead to sudden thrombosis development. Explain why the low-grade inflammatory process may lead to the fibrous cap becoming unstable. Cardiovascular Pathophysiology I  Case Scenario Mr JD is a 65-year old man. He is overweight, has a history of hypertension, high LDL-cholesterol levels and is a smoker. He has been admitted to hospital with a history of chest pain that developed with minimal exertion. Blood tests and ECG analysis demonstrate no myocardial infarction. The doctor told him he had ‘hardening of the arteries’ and that he now has angina. This patient has a history of hypertension. Hypertension is known to increase the risk of atherosclerotic cardiovascular disease including angina. 7. Write a pathophysiological ‘narrative’ that explains why plaque formation in a coronary artery leads to pain with exercise. Go on to explain why a sudden thrombus may lead to myocardial death. 8. Describe what is meant by the term myocardial infarction. CVD 9. What are the signs and symptoms of myocardial infarction? Tute 2 Cardiovascular Pathophysiology I  Case Scenario Mr JD is a 65-year old man. He is overweight, has a history of hypertension, high LDL-cholesterol levels and is a smoker. He has been admitted to hospital with a history of chest pain that developed with minimal exertion. Blood tests and ECG analysis demonstrate no myocardial infarction. The doctor told him he had ‘hardening of the arteries’ and that he now has angina. This patient has a history of hypertension. Hypertension is known to increase the risk of atherosclerotic cardiovascular disease including angina. 10. Provide a short definition of heart failure CVD Tute 2 11. Describe the MAIN compensatory mechanism associated with heart failure 12. How the early compensatory mechanism can eventually contribute to the pathogenesis of heart failure Cardiovascular Pathophysiology I