PSIO 303B Exam 3 Learning Objectives PSIO 303B Exam 3 Learning Objectives PSIO 303B Exam 3 Learning Objectives PSIO 303B Exam 3 Learning Objectives Unanswered Learning objectives are answered within my handwritten notes in a much more meaningful and integrated fashion Lecture 32 Cardiac Cellular Physiology 1 Distinguish between CHF as a Syndrome as compared to a disease like catching a cold Change of morphology as a result of increase in load Disease Syndrome 2 List at least 3 causes for CHF Endocarditis 3 Define Cardiac remodeling Coronary Artery Disease Atherosclerosis hypertension Alcohol Abuse Valvular disorders After initial insult Myocardial Infarction Pressure Overload Concentric H Volume Overload Eccentric H there may be necrosis and disproportionate thinning in one area resulting in an inability to handle pressure and volume in the same manner as the rest of the healthy tissue This can initiate cellular signaling in the area In Hypertrophy there is a change in the geometry of cardiomyocytes as a result of one or both of the following 1 transient increase of Ca2 o Distortion of microarchitecture hypertrophic cells impaired coupling distorted spacing between the Cav 1 2 L type Ca2 channel in plasma membrane and the RYR2 Ca2 release channel o Depletion of calstabin 2 results I leaky RYR2 channels continually releasing Ca2 into cytosol High Ca2 Prone to sudden death arrhythmias and delayed afterdepolarizations o MLP muscle LIM protein is a mechanical sensor that triggers HCM by a phosphorylation cascade of protein kinases activating transcription factor AP 1 i Raf 1 Kinase ERK extracellular signal regulated kinase and 2 Mechanical Factors SAPKs MAP kinases ii o Increased levels of i mRNA for actin normally expressed in fetal ii Increased VEGF angiogenic factor 3 awef to affect cellular remodeling to increase fibroblast activity in the area changing collagen synthesis from type 1 type 3 more ridged less compliant Also cardiomyocytes can hypertrophy to deal with the increase in load but become less energy efficient in the process Over time this can change the overall geometry of the cardiomyocytes leading to organ remodeling In this case the heart can become hypertrophic and or Dilated in response to this increase in long term load 4 Identify the underlying cause of familial hypertrophic Cardiomyopathy Mutations in various sarcomeric genes are associated with HCM DCM leading to sudden Cardiac Troponin T 30 years old 41 and Tropomyosin 1 23 years old cardiac death SCD 60 Many mutations in the troponin family PSIO 303B Exam 3 Learning Objectives Lecture 33 Cardiac Muscle Structure and Ultrastructure 5 Identify the 4 chambers of the heart Left and Right atria Left and Right ventricles 6 Trace the Path of blood through the heart and throughout the body Superior Inferior Vena Cava Right Atrium Tricuspid Valve R Atrioventricular Right Ventricle Pulmonary Valve Semi lunar Pulmonary Artery Lungs Pulmonary Veins left right Left Atrium Bicuspid Valve Mitral L Atrioventricular Left Ventricle Aortic Valve semilunar Aorta Brachiocephalic trunk Left Subclavian Left Common Carotid artery and Descending Aorta further systemic circulation 7 List the 3 components of ventricular remodeling adaptation Disease Progression Cellular Biochemical Ultrastructure Histological Genetic Molecular blood Normal 8 Differentiate between fiber orientation in the endocardium compared to the epicardium Heart contracts twists as a result of cardiomyocyte orientation to maximally eject Endocardium superficial Clockwise spiral fibers Epicardium deep Longitudinal Fibers Hypertrophic Diastolic filling is compromised leading to heart failure Endocardium superficial Clockwise spiral fibers Epicardium deep Anti clockwise spiral fibers 9 List the major non myocyte cell type and describe its function Fibroblasts They synthesize collagen in the ECM of the heart The collagen in a healthy heart is elastic compliant enough to allow expansion but will not expand past the optimal sarcomere length 10 Describe the function of the ECM in the heart and how it relates to collagen s in the 3D structure of collagen changes the phenotype 5 types of collagen found in the Heart I III IV V VI Healthy Heart mostly Types I more elastic and Type III more ridged due to cross linking Derived from many genes alternative splicing Disease stimulus Synthesis of collagen shifts isoform expression from type I to type III collagen elasticity 3 4 Pressure in Ventricle due to compliance 11 Collagen Synthesis Translation of mRNA with signal polypeptide on RER Cytoplasm RER Procollagen N terminal removal Hydroxylation covalent modification of Proline and Lysine residues begins at the C Preprocollagen Pre N terminal is cleaved as soon as it enters the ER terminus main goal in establishing orientation Glycosylation of Lysine s in ER Protein disulfide isomerase work together with lysyl oxidase enzymes Help with triple helix formation give structural integrity Increased hydroxyproline content more rigid via hydroxylation enzymes Triple helix formation due to isomerase covalently linking disulfide bonds Moves to Golgi for secretion PSIO 303B Exam 3 Learning Objectives Proteolytic Cleavage in order to leave the cell forms larger fibrils matrices once outside the cell Covalent cross linking Intramolecular Intermolecular forming a collagen fibril 3 D Structure Collagen Fibril Pathological Conditions Myocardial Infarction Chagas Dialated cardiomyopathy Collagen loss 0 4 days Collagen Accumulation 6 Necrosis leads to phagocytes recognizing DAMPs 18 days Crosslinking increases 2x or 3x increase in hydroxyproline pathology 1 Isomerase cellular level Regions of the heart have fibrotic regions contributing to that Understand the enzymes and what they do Covalent Modifications Fibronectin RGD Fibronectin bind integrin bind matrix to a cell Non myocytes mostly fibroblasts produce collagen Myocytes contribute most number ECM and Fibroblasts signal into the cell Laminin bind the matrix and the cell via integrins Mutation and its consequence Lecture 34 Cardiac Muscle Structure and Function 12 Compare and contrast Diastole and Systole Diastole a cycle PSIO 303B Exam 3 Learning Objectives Period of time Ventricular Relaxation passive filling and atrial kick Preload associated with End Diastolic Volume Ventricular Isovolumic ventricular contraction constant volume Pressure Systemic Diastolic mmHg Systole Period of time Ventricular Contraction when ejecting blood Pressure