Exam 3 Flashcards
What are the structures of the vascular system?
o Heart o Arteries (leaving the heart) o Veins (returning to heart)
What are erythrocytes?
red blood cells
What are leukocytes?
white blood cells
What are thrombocytes?
platelets
What are the functions of the blood?
o Respiratory: delivers oxygen to tissues
o Nutritive: delivers metabolites to tissues
o Excretory: removes waste products
o Regulatory: transports hormones, regulates temperature and osmotic balance
What is the general path of blood through the body and how is it affected by age?
• Right side of heart pumps blood to the lungs to be oxygenated and the left side pumps oxygen rich blood to the body. With reduced blood flow as a major factor underlying age=-related decline in many organs and tissues
How explicitly does the blood flow?
o BLOOD ENTERS HEART=> o Superior/inferior vena cava o Right Atrium o Tricupsid Valve o Right Ventricle o Pulmonary Valve o Pulmonary Artery => LUNGS o Pulmonary Vein o Left Atrium o Mitral (bicuspid) Valve o Left Ventrical o Aortic Valve o Aorta o =>TO THE REST OF THE BODY
What is systolic pressure?
Heart beats, ejects blood, this pressure in the arteries causes valves to open
What is diastolic pressure?
Heart at rest, this drop in pressure causes the valves to close
What are the non-modifiable risk factors associated with the leading cause of death in America?
are family history, sex and age (cardiovascular disease increased with age)
What are the modifiable factors for heart disease?
hypertension, diabetes, high LDL cholesterol, obesity, drug/alcohol use, poor diet, sedentary behavior and stress.
What are the age-related changes to the cardiovascular system?
o Increase in left ventricular (LV) hypertrophy with an increase in size
o Decline in diastolic function
o Preserved systolic function, but decline in exercise capacity believed to be due to less diastolic pressure
o Increased atrial fibrillation with uncontrolled, dis-synchronous beating
o Increased LV (left ventricular) wall thickness less elasticity
o Decreased LV filling during end diastole
o Increased mitral inflow (valve between atria and ventricle in left side) (E/A ratio), indicating diastolic dysfunction meaning that there is flow back into the atrium
o Aged-heart
What does decreased LV filling during end diastole do?
Decreased elasticity
Increased LV fibrosis stiffness
Therefore, relies on an increased contribution from atrial contraction— may lead to an increased risk of atrial fibrillation
What is the aged heart?
Results in a compromise in the cardiac capacity
Lowers the threshold for development of heart failure
Increases susceptibility to stresses and disease-related challenges
Ultimately contributes to heart failure
What are some age-related cardiovascular disorders?
arteriosclerosis leading to ischemic heart disease, hypertension, hypotension, coronary disease, gain pectoris, myocardial infarction, congestive heart failure, and heart valve disease
What is arteriosclerosis?
➢ All individuals have buildup of plaques with age
➢ Composed of LDL(bad cholesterol): HDL (can remove LDL from arteries and doesn’t built up) can scavange
➢ Athersclerosis: plaque creates blockage and disrupts blood flow it also activates the immune system.
What is ischemic heart disease?
➢ Ischemia: If athersclerosis is severe enough, blood flow can be blocked- death of tissue
➢ Occurs when a large artery in the heart, becomes blocked by an athersclerotic lesion and blood flow to heart decreases
➢ If blockage reduces flow more than 85%, cardiac tissue death will occur
➢ Myocardial infarction (Heart attack)
What is hypertension?
> 140/90
Increased risk of cardiac arrest, stroke, vascular disease, kidney disease, macular degeneration
What is hypotension?
(postural):
What is coronary disease?
Blood supply to cardiac tissue is slowed/blocked by aneurysm, hemorrhage, clot, plaque
What is angina pectoris?
“chest pain”
Acute coronary event
What is a myocardial infarction?
Heart attack
Hypoxia in cardiac tissue due to acute oxygen deprivation
“classic” symptoms: radiating chest pain affecting jaw, neck, arm
“silent” symptoms: digestive disturbance, fatigue, dizziness
What is congestive heart failure?
chronic deterioration of the heart
Systolic: incomplete pumping out of heart into lungs
Diastolic: inadequate pumping out of lungs
What is heart valve disease?
Stiffening/malfunction of heart, pulmonary, aortic valves
What is the P wave in an electrocardiogram?
record of atrial depolarization
What is the QRS complex?
record of movement of ventricular depolarization
What is the ST segment?
corresponds to the time when the ventricle is contracting but no electricity is flowing through it. The ST segment usually appears as a straight, level line between the QRS complex and the T wave.
What is the T wave?
corresponds to the period when the lower heart chambers are repolarizing.
What are the four types of dysfunction found?
Ejection fraction o Diastolic dysfunction: Mitral Inflow: E (filling of the ventricle) /A(filling of atrial expect only a little filling of the mitral valve but if large inflow back have a lot back in atrium) ➢ Blood flow across the mitral valve is assessed with dopplar, 2 waves are seen: ➢ E wave (filling of ventricle) ➢ A wave (filling of atrial) Thickened ventricle Cavity size o Wall motion abnormailty o Valve assessment o Hypertrophic cardiomyopathy LVMI: Left ventricular mass index
What are the cardiovascular measurements?
o Speckle-tracking strain image analysis
Myocardial deformation
Regional variation in wall synchronicity indicative of ventricular function
*uses speckle tracking algorithm to monitor the deformation of the endocardium
*Measures the shortening of the cardiomyocyte (strain) and the rate at which this deformation occurs (strain rate)
*shown to be more sensitive to regional variation in ventricular function
How does mitochondria play a role in cardiac aging?
o Heart has high energy demand, therefore, rich in mitochondria => susceptible to oxidative damage
o Overexpressing catalase in the mitochondria with a decreased LMVI.
o E/A ratio diastolic disfunction protecting free radical production protects form age-related declines
o Polg mice: homozygous mutation in mitochondrial polymerase (proofreading for mutations) gama causing increases in mitrochondrial DNA mutations
o MCAT shows better with the mutated mouse.
Protecting from reactive oxygen specie sin the mitochondria specifically leads to increased life span.
Looking at left ventricular mass, hypertrophy with age and wild type see increase in left ventricle size. overexpress catalase protecting from increase so not increasing as much as the wild type.
As a measure of diastolic disfunction measuring E/A ratio where they see wild type with age increase in diastolic dysfunction. increasing catalase in the mitochondira leads to less diastolic disfunction although it does increase with age.
What is accelerated age-dependent cardiomyopathy poll m/m mice?
Homozygous mutation of mitochondrial polymersaase gamma
mutation leading to decreased proofreading capabilities
leads to substantial increases in mt DNA mutations and deletions.
Polyg m/m mice display an accelerated cardiac aging phenotype that is rescued by overexpressing mCAT. With age greater increased in ventricular mass and don’t see a statistically significant increase in the wild type mouse. increased cardiac aging types with. Don’t see increased in left ventricular mass in wild type, mCAT significantly decreases on the double mutant suggesting ROS playing role in aging heart.
E/a Ratio shifting to the lower ratio indicating diastolic dysfunction with age.
Polgm/m myocytes display increased cellular senescence and apoptosis that is rescued by overexpressing mCAT.
How does nutrient signaling affect cardiac aging?
o Rapamycin Protects Against Cardiac Hypertrophy Induced by Angiotensin II. Angiotensin II: Hormone that causes vasoconstriction and increase in blood pressure that ultimately leads to heart failure. Aldosterone can also lead to fibrosis less contractability and less heart function.
o Rapamycin Protects Against Angiotensin II-Induced Increase in Protein Synthesis. Rapamycin inhibits the activation of S6 that leads to increase protein synthesis associated with cardiac hypertrophy! Increased phosphorylation of S6, treating with rapamycin with increasing doses large increase in phsophoryaltion of S6 and rapamycin suppresses the increases. reduction in S6 phosphorylation reducing cardiac hypertrophy seen in this model
o Rapamycin suppresses pressure overload-induced increase in myocyte size. Did surgery to restrict aorta. Show an increase in ventricular size and an increase in myocyte size showing hypertrophy. With rapamycin inhibiting tor in control no difference, and reduce size of myocytes for those that had surgery.
o Rapamycin: reduced cardiac inflammation and improved cardiovascular functions (LV function and cardiac hypertrophy). Looking specifically at the E/A ratio. Better contraction and a better release.
o Young mouse have rapamycin and calorie restriction improving cardiac function in old muce. Improved E/A ratio with calorie restriction. Attribute to better mitochondrial function and biogenesis.
What does inhibiting mTOR in cardiac hypertrophy do?
Protects against cardiac hypertrophy and age-related decline in LV Function
Mechanistically:
Inhibits protein synthesis, potentially reducing the increased size of myocytes seen with age
Enhances RAD expression (unclear if direct target of mTOR). calcium signaling inhibiting hypertrophy.
Similar cardiac improvement as Calorie Restriction
What is the hormonal regulation of cardiac aging
angiotensin-aldosterone system
adrenal signaling
insulin signaling
o
How does insulin signaling affect cardiac aging?
In mice, decreased insulin signaling attenuates age-associated cardiomyocyte dysfunction. In isolated cardiomyocytes ability to contract on a dish in response to insulin.
In contrast, in humans, there is a decline in serum IGF-1 with age that correlates with an increased risk of heart failure! Increasing IGF-1 in humans may be beneficial under conditions of heart failure.
What are some general structural age=related heart changes?
Pericardial fat accumulation Coronary blood vessel rigidity Collagen/elastin increase Decreased contractile deficiency Lipofuscin accumulation Heart valve thickening Pacemaker cell number decline Vein dilation and stretching Coronary artery integrity weakens
What are some general functional age=related heart changes?
Longer beat recovery required Increased incidence of arrythmia Skipped/extra beats Cardiac output (blood vol/min) decline Increased incidence of fibrillation and electrical impulse block Increased blood vessel rigidity Slight plasma volume decreases
What occurs in atherosclerosis?
Inflammatory Response Formation of Foam Cells Foam Cells Weaken Arterial Wall Over time, plaque calcifies Can be released and cause blockage (embolus)
What is doppler imaging?
Estimates blood flow velocity using frequency changes
What is mitral inflow?
E/A Blood flow across the mitral valve is assessed with dopplar, 2 waves are seen: E wave (filling of ventricle) A wave (filling of atrial) Thickened ventricle Cavity size Wall motion abnormailty Valve assessment Hypertrophic cardiomyopathy LVMI: Left ventricular mass index
What occurs in the physiology of normal aging?
Changes in Body Composition ( increases in fat as you age with a decline in physical activity and a decline in food consumptiona) nd Energy Metabolism (muscles utilize half resting energy expenditure with reducing mass reducing metabolism) Decreased Muscle Mass: Sarcopenia Changes in the Skin Changes in the Senses: such as Hearing: presbycusis and Vision: presbypia, cataracts Changes in the Digestive System Changes in the Immune System Changes in the Reproductive System
What is Sarcopenia?
loss of muscle cell number and cell size
What is type I muscle?
slow touch endurance type activites such as running a marathon and maintain posture antigravity muscle
What is type II muscle?
fast twitch with short-term intense or powerful movements such as hitting a baseball and they decrease the most with age.
What happens in normal skin aging?
Loss of subcutaneous fat, Thinning dermis, and Loss of collagen fibers (providing structure to dermis
What is presycusis?
o Primary cause of the age-related decline in hearing is alterations to the inner ear: Loss of hair cells, Loss of stereocilia in the organ of Corti (Reduced release of neurotransmitters resulting in decreased ability to detect l and loudness and higher pitches).
What is presbyopia, cataracts?
inability to focus on close objects and it Affects ALL individuals over the age of 50, Due to inability to replace or repair damaged cells in the lens and collagen becomes stiffer with age
What are cataracts?
opacity in the lens of the eye: At the interface between normal aging and disease, and May be due to reduced Unfolded Protein Response with age!
