BIOE 2010 Week 7/8 Notes
BIOE 2010 Week 7/8 Notes BIOE 2010
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This 15 page Class Notes was uploaded by Sara Littlejohn on Thursday October 13, 2016. The Class Notes belongs to BIOE 2010 at Clemson University taught by Dr. Alexis and Dr. Webb in Fall 2016. Since its upload, it has received 15 views. For similar materials see Intro to Biomedical Engineering in Bioengineering at Clemson University.
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Date Created: 10/13/16
Medical Imaging What is medical imaging? Seeing inside the body non-invasively In 2d: pixels In 3d: voxels Modalities o Different types of imaging can be classified as different modalities typically by the methods used and the overall goal of the imaging methods o Types of modalities: X-ray CAT scan MRI Functional MRI Ultrasound Light imaging Nuclear Medicine PET scan Wilhelm Rontgen o Physicist (1845-1923) o Research into the effects of electric discharge on vacuum tubes o The tubes were built with a thin aluminum window which was easily damaged by electrostatic charges in the tube, so a piece of cardboard was placed in the tube to protect the window o When a cardboard painted with barium plantinocyanide was placed was beyond the window he noticed it was florescent o Discovered an unknown type of ray and called it an X-ray o He was awarded the first Nobel prize in physics X-ray imaging o Some x-rays have to be absorbed or scattered in order to make an image o In a plan film x-ray photons hitting the film cassette darken the film o As film is clear food attenuators will appear clear and poor attenuators will appear black o We use phosphorescent screens to further darken the film and other devices to provide clean images o Almost no one uses film anymore it’s all digital Controlled Drug Delivery Drug delivery systems can rescue drugs that have failed in clinical trials Most drug’s half-life in the body is short. Extra-Cellular Barriers o Immune system o Blood proteins o ECM o Cells Intra-cellular Barriers o Uptake o Acidic pH o Endosome escape The route of administration affects the drug concentration in the blood. Advantages of Drug Delivery Systems: o Increased patient compliance: less frequent dosing and more acceptable o Safety: can control the dose of drug over time for optimized efficacy o Protect drug from degradation o Increased dose: improve therapy Dispersed drugs have 2 phases because the drug is insoluble o Has lag time because it is not soluble Dissolved drugs have 1 phase because the drug is soluble Controlled Release Mechanisms I.V. Drug Pulsatile Diffusion Fick’ sErosion Law: Dissolved Drug D= Diffusion Coefficient (cm^2/s) Delta is the thickness of the Diffusion is first order Erosion is zero order Higuchi Model: Dispersed Drug A- area of the delivery system D- diffusion coefficient Cs- limit of solubility of the drug inside the film Co- concentration of drug inside the film Erosion Controlled Release Equations Mt/M∞= A Ke t Ke =Diffusion coefficient A=Area Zero Order Tissue Barrier: Intestine Very difficult to pass through the cell layer Blood vessels are connected to the lymphatic vessels. If the drug can pass through the cell layer it has a better chance to get into the blood vessels compared to the lymphoid vessels Smaller tower is composed of endothelial cells and m cells (good at absorbing bc they can transfer things from the intestine directly to the lymph nodes (direct contact with the immune system)) Blood Circulating DDS Nanoparticles have two parts: the inside is called the core and the outside is called the corona Liposomes and polymerases contain a capsule. This allows you to have hydrophobic drugs in the capsule. Conjugated has a chemical link to the drug and those links have to be broken before the drug can come out, making it take longer than the others. Encapsulated Loaded Adsorbed Conjugated Advantages of PEG o To be stable in water, there is a capsule so the drug can be hydrophobic o It reduces the absorption of proteins in the blood by being flexible The drug in the liposome can stay in the blood longer because the particle is bigger Add PEG to that can it stays even longer because it reduces proteins that would bind to the polymer Cardiovascular System The Heart pump using transport medium (blood) Propels substances to body cells o Oxygen o Nutrients o Wastes o Many other substances Circulatory System Systemic circuit o Blood vessels that carry the functional blood supply to and from all body tissues Pulmonary circuit o Blood vessels carry blood to and from lungs Blood-Oxygen Transport Red blood cells transport hemoglobin Hemoglobin reversibly binds oxygen Lungs-high levels of oxygen, oxygen binds to hemoglobin Capillaries-low levels of oxygen, oxygen dissociates from hemoglobin and diffuses into surrounding tissue Structure of the Heart Pericardial cavity filled with fluid for lubrication Myocardium: thickest layer. Cardiac muscle, collagen and elastin, Endocardium: continuous with blood vessels- endothelial cell lined- prevents blood clotting on the wall Myocardium and Endocardium Myocardium-composed of cardiac myoblasts (cardiomyocytes)- contraction and relaxation Endocardium-endothelial cells-provide a “perfect” blood contacting surface that does not initiate coagulation Chambers of the Heart Atriums o Receiving chambers o Relatively small, thin-walled chambers o Blood only pushed to ventricles Ventricles o Discharging chambers o Make up most volume of the heart 4 chambers o Right atrium (Blood from body) o Right ventricle (Blood to lungs via the pulmonary artery) o Left atrium (Blood from lungs via the pulmonary vein) o Left ventricle (Blood to body via the aorta) – walls 3X’s as thick as right ventricle Heart Anatomy Atrioventricular valves- o Tricuspid valve o Mitral valve Semilunar valves- o Aortic valve o Pulmonary valve Cardiac Cycle Diastole-heart relaxed, filling with blood Systole-heart contracting, pumping blood Electrical Regulation of the Heart A. Autorhythmicity B. Pathway of stimulation o 1. SinoAtrial node o 2. AtrioVentricular node o 3. AV Bundle o 4. Purkinje fibers Cardiac Conduction SA nodes generates a periodic, automatic electrical impulse (action potential) Travels down the atrial intranodal and intraatrial pathways Slows at the AV node allowing the atria to contract and empty Travels through common AV bundle to Purkinje fibers causing ventricular contraction Monitoring Cardiac Conduction ECG or EKG-electrocardiogram o Heart is in fluid o Fluid transmits electrical activity from the source to the surface of body o Electrodes placed on skin surface measure direction and magnitude of current flow o EKG-2-dimensional representation of this electrical activity Heart Failure Cardiomyocytes-the muscle cells of the heart-are considered post- mitotic (incapable of cell division) Hypoxia (lack of oxygen) leads to cardiomyocyte death Repaired by fibroblasts and scar tissue Lack contractile properties of cardiomyocytes Decrease the mechanical function of the heart as a pump Solutions for Heart Failure Partially damaged-heart still functions but inadequately o Prosthetic ventricles, such as ventricular assist devices (VADs). Severely damaged-heart cannot function sufficiently to support life o Transplantation o Prosthetic hearts (under development) Pacemakers In mitral stenosis, the mitral valve opening is narrowed, and blood flow from the left atrium into the left ventricle during diastole is reduced. In mitral regurgitation, the mitral valve leaks when the left ventricle contracts (during systole), and some blood flows backward into the left atrium. The heart valves can malfunction either by leaking (causing regurgitation) or by not opening adequately and thus partially blocking the flow of blood through the valve (causing stenosis). Either problem can greatly interfere with the heart's ability to pump blood. Sometimes a valve has both problems. Pacemaker Lead Epicardial is better for children because they have small arteries Vascular System Blood Vessels Arteries Capillaries Veins Arteries vs. Veins Arteries o Carry oxygenated blood to tissues o Experience higher pressure o Relatively more muscle / elastic structure – narrower lumen o All arteries possess 3 layers (tunics) Intima (endothelial cells+ ECM) Media (smooth muscle cells+ collagen + elastin + proteoglycans) Adventitia (fibroblasts and immune cells) o Categories Large elastic arteries/arterioles Muscular arteries Veins o Carry de-oxygenated blood to heart o Larger lumen / less muscle / elastic structure o Lower pressure o Valves in major veins prevent backflow Blood Flow Regulation Vasoconstriction: reduction in lumen diameter due to SMC contraction Vasodilation: Widening of the lumen due to SMC relaxation Poiseuille’s Law The Effect of Radius Aneurysm Artery segments which is weakened and then expands enormously Aneurysms may burst with fatal results Management o Vascular graft Atherosclerosis Plaque: Pathological deposition of fatty substances, cholesterol, calcium, and other substances on the vascular lining Cause-uncertain, believed to be related to injury to the endothelial lining Potential sources of injury o elevated levels of cholesterol and triglyceride in the blood – cholesterol is a major component of plaques o Physical stress-high blood pressure o Chemical stress-tobacco smoke / free radicals-oxidized cholesterol can damage vessel wall and initiate inflammatory response o infection Fluid flow during Occlusion Blood restriction-in coronary arteries, insufficient blood supply leads to damage to the heart-eventually require VAD and transplant Plaque breaks free from vessel lining – similar to thromboembolism o Blockage in coronary arteries-heart attack o Blockage in brain-stroke o Blockage of peripheral tissues-necrosis Vascular Repair Necessitated by vascular damage or pathology that interferes with normal blood flow o Vascular graft (biomaterials)-large diameter vessels o bypass (autograft)-small diameter vessels o removal of blockage-angioplasty / stenting (interventional cardiology) Artificial Blood Vessels Very effective for replacement of large diameter vessels (>6 mm) High pressure and flow minimize thrombosis Small Diameter Grafts Biomaterials are not yet successful o thrombosis o intimal hyperplasia colonization of vessel lumen by excessively proliferating smooth muscle cells-leads to narrowing, occlusion, failure Vein Transplants Limitations of ByPass Substantial donor site morbidity-secondary tissue damage at the harvest site Patients with severe coronary atherosclerosis usually have systemic atherosclerosis, so the saphenous vein may not be completely healthy Balloon Angioplasty Percutaneous Transluminal Angioplasty (PTA) Balloon expansion to compress atherosclerotic plaque inside the arteries Embolism-plaque breaks free and enters the circulation Restenosis-re-occlusion commonly due to excessive smooth muscle cell proliferation (intimal hyperplasia) in response to vascular injury (40%)
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