EHR519 Week 4B Pathophysiology, Meds & Vascular/Heart Diseases, 2022 PDF

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Warning This material has been produced and communicated to you by or on behalf of Charles Sturt University in accordance with section 113P of the copyright act (Act). The material in this communication may by subject to copyright under the act. Any further reproduction or communication of this material by you may be the subject of copyright protection under this act. Do not remove this notice Week 4 Lecture 2: Pathophysiology, medications, contraindications and exercise testing and prescription for: ATHEROSCLEROSIS ISCHEMIC HEART DISEASE Angina Peripheral arterial disease Valve diseases Myocardial infarction 2 Learning Outcomes On successful completion of this subject, you should: be able to explain the purpose of graded exercise testing (GXT), the common modes and protocols, and which populations they are used for; be able to describe the relative and absolute contraindications to terminate a GXT; be able to explain the appropriate measures to be recorded before, during and after a GXT, and the normal and abnormal responses; be able to outline the risk factors, complications and comorbidities that must be accounted for when applying exercise interventions to individuals with atherosclerosis, ischemic heart disease and angina; and, be able to describe common treatments, and the effects of commonly prescribed medications on acute and chronic exercise responses that must be accounted for when applying exercise interventions to individuals with atherosclerosis, ischemic heart disease and angina. 3 Atherosclerosis (atherosclerotic cardiovascular disease) 4  Normal Artery Lumen: Channel for blood flow within the artery Endothelium: Inner, single-cell layer of the artery Vasomotion, regulating hemostasis (anti and pro-thrombotic properties) NO In healthy conditions, protects against the development of atherothombosis Media: contains most of the smooth muscle cells plus elastic connective tissues Smooth muscle cells maintain arterial tone (partial vasoconstriction) Receptors for LDLs, insulin and growth factors Adventita: outermost layer of connecting tissue, fibroblasts and a few smooth muscle cells Highly vascularised and provides media and intima with O2 and nutrients 5  Atherogenesis Atherosclerosis = disease process resulting in blood flow limiting lesions in the epicardial coronary, carotid, iliac and femoral arteries, and the aorta Endothelial injury resulting in endothelial dysfunction and a subsequent inflammatory response play critical roles Progression may occur for decades before a clinical event occurs Chronic excessive injury to endothelial cells may be due factors such as: Smoking and chemical irritants Low-density lipoprotein cholesterol (LDL) Hypertension Hyperglycemia and T2DM Plasma homocysteine Infectious agents (herpes) 6  The ED may lead to the following abnormalities characteristics of an inflammatory responses: 1. Increased adhesiveness resulting in platelet deposition, monocyte adhesion 2. Increased permeability to lipoproteins and other substances in the blood 3. Impaired vasodilation, increased vasospasm Platelets adhere to the damaged endothelium (platelet aggregation) → release growth factors and vasoconstrictor substances, such as thromboxane A2 → monocytes adhere to the injured endothelium and migrate into intima → LDL enters arterial wall and undergoes oxidation → Monocytes accumulate LDL, altering the oxidation process and transform into macrophages → form small blood clots on the vessel wall (mural thrombi) These changes indicate a switch in endothelial function favouring a prothrombotic, vasoconstrictive state. 7  Cont…. Growth factors (expressed by platelets, monocyes and damage endothelium) result in Growth and proliferation of certain cells Migration of cells into the area of injury Smooth muscle cells and fibroblasts migrate from media to intima Smooth muscle progenitor cells migrate from bone marrow to intima Some cells, plus monocytes accumulate cholesterol into the extracellular space Creates fatty streaks (earliest detectable lesion of atherosclerosis) Immune system cells, T lymphocytes present in streaks/ contribute to arterial wall inflammation. 8 Cont…. Lesions will progress in complexity and size Fibromuscular plaque which now includes: A fibrous cap, lipids, inflammatory cells such as macrophages and T lymphocytes, smooth muscle cells, thrombus and calcium Arterial remodelling: lesions and atherosclerotic progress thickens the vessel wall without changes lumen size Progression of atherosclerosis will then begin to reduce lumen size and thus reduce blood flow 9 Cont…. Progression of size and volume of lesions is variable Slowly progressing plaques may gradually internalize monocytes and lipids, while rapidly progressing lesions incorporate thrombus into the plaque Local stressors (turbulent blood flow or vasoconstriction) or chemical factors (enzymes that weaken the fibrous cap) within the lesion May rupture plaque or fissuring of the fibrous cap → exposing the internal contents of the plaque to the blood Thrombus can form and be incorporated into the plaque Rupture and thrombus formation can repeat producing several layers to the lesion (advanced atherosclerotic plaques). 10 Tuttolomondo, A., Di Raimondo, D., Pecoraro, R., Arnao, V., Pinto, A., & Licata, G. (2012). Atherosclerosis as an inflammatory disease. Current pharmaceutical design, 18(28), 4266-4288.  Detection of atherosclerotic lesions Selective coronary angiography is the gold standard to identify the severity of coronary lesions. However, the degree is greatly underestimated (except for complete occlusion), because of the diffuse nature of the disease process Obstructive coronary lesions occur most frequently in the first 4 to 5 cm of the epicardial coronary arteries (distal may be seen). Obstructive lesions at origin of the left main and right main coronary arteries. Women lag 5 to 20 yr behind men 15  Risk Factors Tobacco use Elevated plasma homocysteine, an Dyslipidemia, especially elevated LDL-C and low intermediary in the metabolism of the levels of high-density lipoprotein cholesterol (HDL-C) essential amino acid methionine Hypertension Sedentary lifestyle Obesity Fibrinogen, a protein factor in the blood Diabetes mellitus coagulation cascade Metabolic syndrome (a combination of conventional risk factors associated with obesity and insulin resistance) Lipoprotein(a) Family history of premature coronary disease (male first-degree relatives