Biology of Aging: Cardiovascular, Respiratory and Urinary Systems

Home , Urinary system

Cardiovascular, Respiratory and Urinary Systems

● Introduction

❍ Cellular Basis of Aging - General Information ❍ Analysis of Physiological Systems

● Websites

Lecture Part I: The Cardiovascular System

Lecture Part II: The Respiratory System

Lecture Part III: The Urinary System

Objectives

● Be able to define, distinguish, and describe normal age-related biological changes of the respiratory, urinary, and immune systems ● Be able to discuss the impact of age-related changes on the needs and functioning of older adults

● Understand how normal age-related changes influence the older person's ability to function ● Be able to distinguish normal age-related changes from disease processes ● Be able to distinguish between chronic and acute disorders ● Be able to define and discuss common disorders that come with age of the major body systems

Introduction

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One of the great scientific challenge's of the 21st century will be to unravel the biological basis of the aging process and through that knowledge to develop strategies for slowing the rate of senescence and increasing the years of healthy living. Researchers are faced with a problem, however. Aging is a deteriorative process upon which pathology and disease are superimposed. Aging and disease can produce the same physiological outcome and, in a sense, aging can be considered the soil from which

diseases arise. It is therefore a difficult task for gerontologists to isolate the effects of "normative" aging. Consequently, we can only tentatively draw demarcations between aging, degenerative processes and disease. Categorization of "normal" aging is clouded further by the similarities that exist between changes associated with aging and those observed with disuse (i.e. bed rest and space travel). It is also clear from our previous discussion on "successful aging" that social, psychological, and biological consequences of "life styles" can also dramatically influence how we age.

Cellular Basis of Aging - General Information

Our bodies are in a constant state of flux. The cellular changes that occur may be a response or adaptation to new conditions (i.e. growth in muscle mass in response to weight lifting) or they can reflect the daily maintenance of the cell's compliment of lipids, proteins and nucleotides (mRNA and DNA). Optimal maintenance of cellular and tissue functioning requires a tight homeostatic control of cellular and tissue renewal.

At the single cell level, this includes the elimination of bad, tattered proteins and their replacement with newly synthesized proteins (a process referred to as protein turnover). Generally speaking, in all tissue examined age causes a slowing down of the process of protein turnover. The functional consequence is a reduction in the performance of the job allocated for each class of protein. Proteins perform many duties including the movement of water and ions in and out of cells, the production of energy from the metabolism of sugars and the repair of damaged DNA found within the nucleus of each cell.

Some tissues not only renew themselves through protein turnover, but they also undergo renewal through cell replacement produced by cell division. Examples would be fibroblast cells found in the skin, immune system cells and cells of the lung and gastrointestinal tract. There are a couple of key tissues that do not undergo cell division, however. These include the cardiac myocytes of the heart, the myofibers of your skeletal muscles and the nerve cells found within the central nervous system. For those tissues that do use cell division for renewal an important consequence of the aging process is the age-related slowing that occurs in the rate of cell division. Much like the effect of slowed protein turnover, the slowing in cell division can result in a less then optimal collection of cells present for performing the job designed for that tissue.

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Cellular Basis of Aging - General Information

including the movement of water and ions in and out of cells, the production of energy from the metabolism of sugars and the repair of damaged DNA found within the nucleus of each cell.

Analysis of Physiological Systems

The following lecture, as well as next week's lecture will discuss each of our physiological systems separately. It is important to remember, however, that they do not act independently, but rather they all work in concert. For example, the urinary system maintains a tight control over the fluid levels found with in our bodies, which directly effects the performance of the cardiovascular system through maintenance of optimal blood pressure. Cardiovascular performance, in turn, directly influences the performance of all tissue through the optimal delivery of nutrients and oxygen. A breakdown in one system can cause a domino effect, resulting in compromise or failure in other systems. When appropriate, these types of potential interactions between the physiological systems will be referred to.

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It is also important to note that throughout modern history scientists and clinicians have developed interventions to combat disease and, as a result extend the life span. At the turn of the 19th century, the focus

was on infectious diseases and with the advent of antibiotic therapies and the development of vaccinations we were able to significantly reduce the morbidity and mortality associated with these infections. Consequently, people began to live longer and, associated with the increase in life span, there was a dramatic increase in the incidence of chronic diseases linked to long-term survival. These diseases or conditions are referred to as age-related diseases. Take a look at the leading causes of death for Americans over 65 (from the Center for Disease Control). As you can see, the most common cause of illness and death in older populations is cardiovascular disease, a chronic disease that develops and progresses through the life span. It is therefore, appropriate that we begin our discussion of aging and system physiology with the cardiovascular system.

Websites

For your information, the following links have been added:

HON Dossier on Ageing http://www.hon.ch/Dossier/Ageing/part2.html

The Challenge Project http://quest.arc.nasa.gov/space/challenge/background/pp. html

Click here to go to Lecture Part I: The Cardiovascular System

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Cardiovascular, Respiratory and Urinary Systems

Part I: The Cardiovascular System

● Cardiovascular System - Normal Aging

❍ The Heart

❍ Aging in the Heart

❍ The Vasculature

❍ Vascular Changes with Aging ● Atherosclerosis

● Clinical Intervention for Cardiovascular disease ● Websites

● Key Points

Lecture Part II: The Respiratory System

Lecture Part III: The Urinary System

Cardiovascular System - Normal Aging

The cardiovascular system is composed of the heart, the blood and the vasculature. This system subserves many functions, most notably the delivery of oxygen throughout the body. The cardiovascular system also serves as a roadway for delivering:

1. energy containing molecules like sugars and fats to needy tissues, 2. amino acids and nucleic acids for the synthesis of new proteins and DNA, 3. toxins and waste to the kidneys for elimination from the body, 4. hormonal messages to distant target tissues, 5. immune system cells to the site of foreign molecules, 6. blood to and from the surface of the skin for regulating body temperature.

Each of these functions is minimally affected by age, but they can be severely altered by interactions that occur between aging and age-related diseases in the cardiovascular system.

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Before we attempt to dissect out the physiological changes that can be accounted for by aging, we need to eliminate from the sample individuals experiencing varying degrees of disease. Human studies of cardiovascular aging are limited by the prevalence of occult coronary stenosis, with 60% of men over the age of 60 having a 75-100% block in at least one coronary artery. Through rigorous screening of coronary disease and elimination of those with coronary artery disease, it has been demonstrated that cardiovascular reserve capacity decreases with aging. These changes in cardiovascular function can be explained by changes in cardiac muscle, connective tissue, cardiac adrenoreceptors, and the compliance or distensibility of the vasculature. In addition, there are changes in kidney function which can alter fluid homeostasis and contribute to age-dependent reactions to therapies for cardiovascular conditions.

The Heart

The contractile muscle of the heart is made up of a special type of cell referred to as a cardiac myocyte. These highly contractile cells have an enormous appetite for oxygen and glucose. These cells never rest, from the day of fetal formation to the last day of your life. The cardiac myocyte is also unique in that it is electrically coupled to neighboring cardiac myocytes. This property facilitates the simultaneous contraction

of all myocytes during either atrial or ventricular systole (systole is the contracted state of heart muscle). There are numerous arteries that go directly from the aorta (the first major blood vessel leaving the left ventricle) to the heart to ensure the rapid delivery of oxygen and glucose to working cardiac muscle. These blood vessels are called the coronary arteries. There is an intrinsic, self-sustaining mechanism (a pace maker) that sets the strength of each contraction and the number of heart beats per minute, but both of these can be modulated by hormones and neurotransmitters found within the body.

Aging in the Heart

With aging, a few functions are preserved. For example, the cardiac output (the amount of blood pumped per minute) is not changed. But the efficiency of pumping the blood does change. More blood is left in the heart after a contraction, the thickness of the major pump, the left ventricle is increased and the response to stimulation of the heart rate is diminished. As a result, the maximum heart rate decreases with aging. Therefore, when we exercise, the maximum heart rate decreases by 1 for each year of aging (i.e., maximum heart rate at 20 is 200 and at 70 is 150). Functionally, these "normal" age-related changes are unlikely to compromise everyday living, but they will reduce the maximal performance. This can occur due to the demands placed upon the cardiovascular system during competitive exercise are greater in old age.

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The Vasculature

The aorta and much of the arterial tree function as an elastic buffering chamber that act to dissipate the pressure wave resulting from ventricular contraction (systole). During diastole (resting state of the heart), the large arteries supply the volume of blood to the periphery as a continuous peripheral blood flow. The diameter of the individual arteries steadily decreases as you move away from the heart. With each successive branching of the artery the diameter decreases, but the sum of the cross sectional areas of these branches gradually increases and, thus, the rate of blood flow and blood pressure diminishes as the blood approaches the capillaries. The arteries and veins are multi-layered cylinders, with each layer serving specific functions. The thickness of each layer is far greater in the arteries, however.

Blood Pressure for Average, Aged, and Diseased Arteries (on the average)

At Maximum Animated Comparison Rest Flow Diagram

Average 80 110 Average Artery

Click here for Aged 110 140 Aged Artery Comparison

Diseased 110 180 Diseased Artery

Vascular Changes with Aging

With aging, there is a thickening of the artery walls. In hypertension, these normal age-related increases in

the large arteries are enhanced. The generic term, arteriosclerosis, refers to a thickening and hardening of the arterial wall. Taken together, these age-related changes all contribute to an increase in systolic blood pressure, which makes age a risk factor for hypertension.

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Atherosclerosis

Atherosclerosis (not to be confused with artherosclerosis) is the leading cause of death in the United States and it affects mainly the large arteries to produce coronary artery disease (CAD), peripheral artery disease in the lower extremities and cerebrovascular disease (stroke). Specifically, atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner walls with eventual obstruction of blood flow. Atherosclerosis begins early in life and progresses slowly over the years, resulting in an exponential increase in vascular related clinical problems. The expression of atherosclerosis is a function of genetic vulnerability, environmental exposure, and a function of the aging process.

Risk Factors

A person presenting with multiple risk factors is more likely to develop atherosclerosis. The risk factors can be divided into the categories of reversible and nonreversible. Nonreversible risk factors include a positive family history of atherosclerosis (genetics), your gender (male, or female), and the aging process. Reversible risk factors include obesity, cigarette smoking, stress, diabetes, inactivity, and hypertension. Another risk factor that straddles these two categories is elevated blood fat levels. Increases in blood triglycerides and cholesterol are associated with age, obesity and familial (genetic) hyperlipidemia.

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The Role of Lipoproteins

The function of lipoproteins in the cardiovascular system is to 1) transport fats in the form of triglycerides and cholesterol to needy cells and to 2) remove excess fats for delivery to the liver. These two distinct functions are mediated by two separate classes of lipoproteins: low-density lipoproteins (LDLs) and high- density lipoproteins (HDLs). Specifically, LDL transports cholesterol from the liver and diet to peripheral tissues, VLDL (very-low density lipoprotein) transfers triglycerides from the liver to peripheral tissues, and HDLs carry cholesterol away from peripheral tissue and deliver it to the liver where excesses are secreted into the intestine as bile. High levels of cholesterol in the diet and thus the blood stream stimulate the liver to increase the synthesis of LDLs.

High levels of LDLs can create enough damage to the endothelial surface so as to increase their entry into the arterial wall. Once there in high concentration, the cholesterol-rich LDLs overwhelm the ability of smooth muscle cells and macrophages to metabolize them. The cholesterol-rich LDLs begin to accumulate and, through activation of LDL receptors, they stimulate the proliferation of arterial smooth muscle cells. This process, in conjunction with migration of macrophages and abnormal layering of new matrix, constitutes the formation of atheromas (atherosclerotic plaques). The combination of decrease in arterial flexibility associated with the fibrotic plaques and the decrease in lumen diameter from accumulation of the plaque (stenosis) causes a dramatic increase in blood pressure above and beyond that expected with aging. At this point the patient would be considered hypertensive (i.e. systolic 190 and diastolic 110), and they would be at risk for the formation of large bulges in the arterial system referred to as aneurysms. Aneurysms, or weakness in arterial walls, are known as silent killers since they almost always result in death when they burst. Atherosclerosis also can result in arterial stenosis and ultimately block blood flow (infarct). If it occurs in the heart, the result can be a heart attack. In the brain, a large blockage causes a stroke and multiple small blockages cause dementia. If it occurs in the kidney, it can result in renal failure. Lipid-related risk factors for the development of atherosclerosis and the associated sequelae are as follows:

● Serum total cholesterol > 200 mg/dL (100 ml) ● Serum total HDL-cholesterol < 35 mg/dl ● Serum total cholesterol/serum total HDL-cholesterol (ratio) >5.0 ● Serum LDL-cholesterol/serum total HDL-cholesterol (ratio) >3.6 ● Serum total triglycerides >109 mg/dl

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Risk Factors of Cardiovascular Disease

Aging: In addition to the before-mentioned changes in elastin and collagen, aging is associated with an increase in blood cholesterol and LDL-cholesterol. HDL-cholesterol does not change, however. Serum cholesterol goes from an average value of 155 mg/dl at age 20 to a value of 215 mg/dl by age 65. LDL- cholesterol goes from a value of 95 mg/dl at age 20 to a value of 140 mg/dl by age 65. By contrast, HDL- cholesterol levels tend to remain constant throughout the life span at a level near 55 mg/dl

Obesity: A person is considered obese if their body weight is 30% above the ideal body weight set for their height. Similarly, a BMI of greater than 22 indicates obesity.

Diabetes mellitus: Increased blood glucose stimulates arterial wall thickening and accelerates formation of plaques.

Cigarette smoking: Smoking increases risk for death from coronary artery disease (CAD) by 75%. The risk of death after cessation of smoking approximates that of nonsmokers at 1-5 years after stopping smoking. Evidence also suggests that second hand smoke doubles the incidence of heart disease.

Stress: The acute effects of stress are to increase heart rate and blood pressure through the release of adrenaline.

Exercise: Exercise has a direct effect on blood vessel walls in the production of elastin and collagen. It also increases HDL and decreases LDL levels. A reduction in body fat caused by chronic exercise also positively influences LDL and HDL levels.

Diet: Fat in your diet directly effects your levels of blood lipids. A diet high in saturated fats and cholesterol stimulates an increase in LDLs. Vitamin E has been shown to be protective for heart disease. Alcohol in moderation may reduce the risk of heart attacks by acting as a mild anti-coagulant. It has also been proposed that the phenols and flavins in red wine may act as clot protecting agents.

Estrogen: Estrogen: Women who take estrogen supplementation therapy (PREMARIN & PROVERA) show reduced LDLs and increased HDLs.

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Clinical Intervention for Cardiovascular Disease

Blood Pressure Reduction There are a number of pharmacological strategies used in the management of individuals with significant atherosclerosis and hypertension. To reduce blood pressure physicians will prescribe either individually or in combination one of the following strategies:

1. ß- blockers: these drugs act by blocking the action of adrenaline on blood vessels. 2. Diuretics: these drugs act on the kidney to decrease blood volume (you end up urinating water that would normally increase blood pressure) (i.e. thiazide diuretics). 3. ACE inhibitors: angiotensin converting enzyme inhibitors block the action of angiotensin, a chemical in your body which constricts blood vessels. 4. Calcium channel blockers (nifedipine, verapamil and ditiazem) - they cause relaxation of blood vessel walls resulting in decreased blood pressure.

Angina, Arrhythmias and Heart Failure Treatments include:

1. Nitroglycerin: used to treat angina (chest or heart pain). It reduces the spasm of arteries. 2. Digoxin: treatment of heart failure and certain atrial arrhythmias. It makes the heart cells operate more efficiently.

Clot Reduction and Elimination Treatments include:

1. Aspirin: one coated, baby aspirin a day is suggested to prevent the formation of blood clots in the heart or brain arteries. 2. Tissue plasminogen activator - tPA (clot buster) is used for the emergency dissolving of blood clots. 3. Heparin - prevents clotting.

Surgical Intervention Surgical intervention involves revascularization of the heart.

Angioplasty Angioplasty involves insertion of an inflatable tube into the artery. The device is guided visually to the site of blockage and then it is expanded to eliminate the block. It is less invasive than coronary by-pass surgery and tends to have less complications.

Coronary Artery By-pass Surgery This operation is designed to increase the blood flow to the heart. It is performed when the major blood vessels that feed the heart, the coronary arteries, have substantial blockage. Blood vessels (usually veins) are taken from the legs and connected to the coronary arteries bypassing areas of blockage.

Website

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American Heart Association http://www.americanheart.org/

Key Points

● The four functions of the cardiovascular system are: transport of blood, nutrients, waste; defense through white blood cells and lymphatic system; temperature control; and acid/base balance (pH). ● Age-related changes of the heart include decreased efficiency, cardiac output and maximum achievable heart rate. However, the heart adjusts to these changes and manages to meet the needs of the body. Arteries lose elasticity (arteriosclerosis) with age, increasing the risk for hypertension. ● Atherosclerosis (plaque formation) is the most common form of heart disease. Other diseases include diabetes (hyperinsulinemia), and congestive heart failure (fluid retention). ● Myocardial infarction (heart attack) results from blocked coronary arteries and usually requires intervention by prescription, angioplasty, or bypass surgery. ● Lifestyle choices (diet and exercise) have profound effects on lipoprotein levels (HDLs and LDLs). High LDL levels are linked with heart disease. ● Cardiovascular disease is the leading cause of death in the United States of those over 65.

Click here to go to Lecture Part II: The Respiratory System

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Cardiovascular, Respiratory and Urinary Systems

Part II: The Respiratory System

● Respitory System - Normal Function

● Aging and Respiration

❍ Mechanical Changes

❍ Diffusional Changes

❍ Defense Mechanisms ● Age-Related Disease in the Respiratory System

● Websites

Lecture Part III: The Urinary System

Normal Function

The respiratory system is a conduit for the exchange of gases between the external environment and our blood. When we think about respiration we focus our attention upon the need to replenish our bodies with oxygen, but another important function is the maintenance of blood carbon dioxide levels and the effect carbon dioxide homeostasis has an blood pH. The organ for gas exchange is the lung, located deep within our bodies. Gases travel through our mouth and nose into the tracheobronchial tree which divides into millions of minute branches terminating in structures known as alveoli. The alveoli are made-up of an incredibly delicate membrane that serves as a fragile barrier between the outside world and our blood. Fragile is the operative word, since life-style choices like smoking or anything that allows the entry of small particles into the lungs can severely damage the membrane and compromise the ability to exchange gases across the pulmonary membrane.

The trunk of the pulmonary tree is the trachea, which divides into two main branches referred to as bronchi. Each bronchi undergoes repeated branchings as bronchioles. The terminal bronchioles branch into alveolar ducts (2-11 ducts) which in turn terminate into alveolar sacs that have 2 or more alveoli. There are approximately 300 million alveoli in the adult lung. Each alveoli is intimately coated with capillaries specialized for the movement of gases into the bloodstream. The combined thickness of the alveolar epithelium and the capillary endothelium is less than 0.2 µm (10-6 meters). An incredibly thin layering of membranes that has evolved to maximize the diffusion of gases between the environment and the blood. The alveoli are the only site for gas exchange in the lung and a key component to maintaining their structure is the secretion of a thin coating of fat (phospholipids) along their outer surface. This coating is known as surfactant and it functions to oppose the natural tendency of bubbles like alveoli to collapse from the surface tension that exists between water and air.

The movement of air in and out of the lungs is voluntarily controlled by messages sent from the brain (medulla) to number of muscle groups, with the lungs acting passively like large rubber balloons. Enlargement of the chest (thorax) during inspiration is produced by a contraction of the diaphragm muscle, located below the lung, and a contraction of the intercostal and pectoral muscles which are attached to the rib

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cage. We exhale by simply allowing these muscles to relax and relying upon the numerous elastic fibers found within the lungs. This passive elasticity allows the lung to recoil to its smaller resting volume. The elastic recoil creates a net positive pressure within the lung to force a percentage of the lung air out. It is this elastic recoil that is most compromised in "successful aging" and as we will see later, it decreases the delivery of new oxygen and the removal of carbon dioxide.

Evaluation of the functional movements of the lung are performed by respiratory therapists. You will be asked to inhale from and exhale into a tube connected to a spirometer (or pneometer) that functions to measure the volumes of air moving in and out of the lung. The following definitions of lung volumes come from such spirometric examinations:

Tidal Air: the volume of air that enters and leaves the lungs during a resting breathing pattern.

Inspiratory Reserve Volume: the volume of air taken in by a maximal inspiration that is over and above the tidal volume.

Forced Vital Capacity: the sum of the tidal volume and the inspiratory reserve volume.

Expiratory Reserve Volume: the volume of air that can be expelled by the most powerful expiratory effort after the tidal volume has escaped naturally.

Forced Expiratory Volume: the sum of the tidal volume and the expiratory reserve volume.

Vital Capacity: the sum of the tidal air and the inspiratory and expiratory reserves (the volume of air expelled by the most vigorous expiratory effort after the deepest possible inspiration).

Residual Volume: the volume of air remaining in the lungs after the strongest possible expiration.

Total Lung Capacity: the sum of the vital capacity and the residual volume.

Functional Residual Capacity: the volume of air left in the lungs at the end of a normal resting, unforced expiration.

Comparison of Normal and Aged Lung Function

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The BLUE represents the amount of air inhaled at any time by a person.

The RED represents the Lungs.

The PINK (below the Lungs) represents the diaphram.

Aging and Respiration

Changes in pulmonary function with age are critical, since severe impairment is a direct risk for death. Aging not only affects ventilation and gas exchange within the lungs, but through compromise in another physiological system -the immune system, it also decreased the ability of the lungs to defend against infectious diseases and toxic insults. In the worst case scenario, the combined effect of age and chronic or acute insults can lead to airway obstruction which increases the risk for death due to:

● Chronic obstructive pulmonary disease ● Cardiovascular disease ● Heart disease ● Stroke ● Diabetes mellitus ● Lung cancer

Mechanical Changes

Age-related changes in pulmonary function, independent of disease or a history of environmental insults, can be accounted for by 1) decreases in lung elasticity, 2) decreases in chest compliance (stiffening of chest wall) and 3) a decrease in the strength of the inspiratory muscles (diaphragm, intercostals, pectorals).

The decrease in lung elasticity is due to the generalized decrease in the turnover and function of the protein elastin throughout the body and the loss of elastic fiber attachments within the lungs. This change in the elastic recoil underlies the age-related increase in residual volume and the decrease in vital capacity. Which means: more stale air remains in the lungs and less fresh air is brought in with each breath.

The decrease in chest compliance is due to an ossification (calcification) of cartilage and rib articulations. The decrease in strength of respiratory muscles is due to a general age-related loss of skeletal muscles fibers http://www.usc.edu/dept/gero/AgeWorks/fall_session/dl/gero500/biology_a_lect/index_b.htm (3 of 6)10/3/07 11:20 PM Cardiovascular, Respiratory and Urinary Systems

with age (see musculoskeletal system in week 8). These later changes contribute significantly to the age- related change in forced expiratory volume.

All of the air flow measures reach a stable maximum between the ages of 20-25 in both sexes. Thereafter linear declines tend to occur, although changes due to attrition of respiratory system tissue are not accountable until age 40.

Diffusional Changes

Age-related decreases in alveolar surface area contribute to a decrease in blood oxygenation. This change is due to a partial collapse of the most distal (peripheral) airways entering the alveoli. These changes can result in a mismatch between the ventilation of the lung and the perfusion of the lung capillaries with blood. This mismatch decreases the diffusion of oxygen into the blood and the movement of carbon dioxide out of the blood. This change is further exacerbated by decreases in cardiac output, which together result in a lowered arterial oxygen content.

The control center for breathing lies deep in the brain in a structure called the medulla. The medullas receives information on blood oxygen and carbon dioxide content from specialized nerve cells known as chemoreceptors located peripherally in nodules known as the carotid and aortic bodies (located on the aorta and carotid artery). There is also evidence that neurons within the medulla react to changes in cerebral spinal fluid pH secondary to hypercapnia (elevated carbon dioxide content). Together, these chemodetectors generate a response which increases both heart and ventilatory rates. With age there is a decrease in these detectors or receptors and thus the response to hypoxia or hypercapnia is diminished as much as 50% in healthy older subjects (65-75 years).

Defense Mechanisms

We use mucus secretion to collect inhaled particulate matter and then we expel the mucus through the motion of ciliated cells found within the bronchioles. When the cilia are overloaded, we rely upon the cough mechanism to expel the mucus. With age, this clearance system is decreased leaving our lung vulnerable to damage associated with mucus obstructions. The cough reflex is further subdued by sedative use and neurologic disease, which are common in the elderly. Once our initial defense mechanism of mucus has been http://www.usc.edu/dept/gero/AgeWorks/fall_session/dl/gero500/biology_a_lect/index_b.htm (4 of 6)10/3/07 11:20 PM Cardiovascular, Respiratory and Urinary Systems

penetrated, we rely upon our immune system to eliminate foreign bodies. As discussed in the immune system section of the course, we have an impaired immune response as we get older that leaves the elderly easier targets to infectious disease in the lungs (i.e. pneumonia and tuberculosis).

Age-Related Disease in the Respiratory System

Age-related disease in the respiratory system: Infections of the respiratory system is the fifth leading cause of death in the United States, with the elderly being particularly vulnerable. As indicated above, the major underlying cause of the increased risk with age is a decline in the immune system's ability to fight-off infection. The elderly are also more prone to aspirating food, which can introduce infection, and they are more likely to be institutionalized, which increases the likelihood for spreading infectious lung diseases. Pneumonia is the most common infectious disease of the lung leading to death. An individual 75 years or greater is at least 5 times as likely to get pneumonia as their 20 year old counterparts, and when they get it they are almost 100 times more likely to die from it. The mortality rate from pneumonia increased 10 fold for each decade of life after the age of 20. Pneumonia can be caused by viral and bacterial infections of the lungs. Some of the more common bacterial infections include pneumococci, gram-negative bacteria and anaerobic bacteria. The major viral infections leading to pneumonia comes from influenza strains.

The most important tool in establishing a pneumonia is the chest X-ray, which can detect the lung infection. This test is followed by an analysis of the sputum for abnormal bacteria. Antibiotic therapy is used to fight bacterial infections, with special care taken to avoid kidney toxicity. The best strategy to be taken for viral infections is prevention. All people, but especially the elderly, are encouraged to be vaccinated each year against the flu. The best viral therapy presently used is amantadine.

A second type of lung infection that targets the elderly is tuberculosis. Tuberculosis is a lung disease caused by a type of bacteria called mycobacterium tuberculosis. Tuberculosis is spread through respiratory secretions emitted by coughing. This bacteria is particularly insidious since it not only infects the lungs, but it also easily spreads to the kidneys and brain. Any condition that reduces the immune resistance will increase the likelihood of tuberculosis infection, sometimes spring from a dormant state from a previous infection. The treatment of tuberculosis is through an extensive use of antibacterial drugs (bactericidal). These tuberculosis is particularly difficult due to the increased likelihood of antibiotic and bactericial resistance.

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Another disease affecting the lungs is broadly described as chronic obstructive pulmonary disease. The most common disease within this category is emphysema. Without argument, the most common cause for emphysema is chronic cigarette smoking. A common symptom is chronic bronchitis with a persistent cough, although not all bronchitis is due to emphysema and not all bronchitis or coughs are due to an underlying obstruction. Cigarette smoking accelerates the age-related decline in forced expiratory volume by 3 fold. The pathology of emphysema is an inflammation of the terminal bronchioles and a destruction of parts of the alveoli.

The most debilitating of lung diseases is also the most frequently occurring form of cancer in the United States, lung cancer. Cigarette smoking is by far the largest cause (in excess of 85% of cases, followed by asbestos exposure). In excess of 175,000 new cases present each year and nearly 150,000 people die annually. Cigarette smoke contains many carcinogens. For example, benzo(a)pyrine is one of approximately 40 known carcinogens found in tobacco. It gets converted to BDPA which directly causes mutations in DNA. Patients with lung cancer are alarmed by an abnormal increase in the frequency and depth of coughing episodes. Another clinical feature is the regular presence of blood in the sputum (hemoptysis). Diagnosis is made by chest X-ray and biopsy. The therapy regime is to remove all tumors through surgery, followed by radiation and chemotherapy.

Websites

Visit these other web sites of interest for information about lung disorders:

American Lung Association http://www.lungusa.org

The National Emphysema Foundation http://emphysemafoundation.org/

Medicine OnLine http://www.meds.com/index.html

Click here to go to Lecture Part III: The Urinary System

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Cardiovascular, Respiratory and Urinary Systems

Part III: The Urinary System

● Introduction

❍ Kidneys

❍ Aging and your kidneys ● Age-related Disease in your Kidneys

❍ Glomerulonephritis

❍ Renal Artery Disease

❍ Chronic Renal Failure

❍ Lower Urinary Tract

❍ Urinary Incontinence

■ Women

■ Men

● Something to Consider

● Quiz #2

Introduction

The urinary system in it's simplest conception functions as our garbage disposal system. However, it's duties are many. It not only cleanses the blood of waste products of metabolism, but it also functions to eliminate foreign substances like prescription drugs. It tightly regulates the fluid levels in our blood stream and thus our blood pressure, and it acts to regulate electrolytes (ions) in our blood stream like sodium, potassium and calcium.

Kidneys

Excretion begins with the kidneys. The blood enters the kidneys through the renal artery which divides into many smaller branches (arterioles) that ultimately form the specialized renal capillary bed referred to as the glomerular apparatus. Each kidney (we have two) has thousands of these capillaries and each capillary has an intimate relationship with a functional unit of the kidney known as a nephron.

The first stage of kidney processing of the blood is filtration of the blood. Large particles like red blood cells and large proteins remain in the capillary bed of the vasculature, while small particles dissolved in the plasma flow out of the blood and into the nephron. An accurate analogy to this form of processing is the use of a colander to strain the water from pasta. When you pour the pasta and water into the colander the water streams through, but the pasta remains behind. The glomerular filtration rate (GFR), which is the rate of filtering the excreted urine, is used to clinically evaluate the functioning of the kidney.

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The basic form of "blood cleansing" produced by filtration is problematic in that there are many desirable compounds which leave the blood and enter the nephron as the filtrate. The descending limb of the kidney tubule has evolved to retrieve these needed biochemicals (i.e. water, sodium, glucose, phosphate, amino acids, sulphate) through a process referred as reabsorption. Some go against a concentration gradient and thus require energy (i.e. sodium), while other compounds like water flow passively through osmotic forces.

The basic filtration process is also inefficient at eliminating some undesirable compounds and thus a second process referred to as secretion has evolved to actively secrete unwanted substances from the blood into the nephron (i.e. acetaminophen, excess electrolytes - sodium and potassium, ). This process occurs after the blood has flowed through the glomerulus and is beginning its trek back to the heart.

The maintenance of body fluid levels is a major function of the kidneys (fluid homeostasis) and as indicated above this is maintained in part through the passive movement (driven osmotically) of water out of kidney tubules into the extracellular space and on into the vasculature. At times this method of water retention may not be adequate and the blood pressure can drop below the desirable homeostatic level. When this happens, sensors located in the hypothalamic region of the brain detect the drop in blood pressure (actually an increase in blood osmolarity) and they secrete a hormone known as antidiuretic hormone or ADH into the blood. The ADH runs through the blood stream to its kidney target where it signals the collecting duct of the kidney tubules to increase the flow of water back into the blood. Another important function performed by the kidneys is to assist in the maintenance of proper pH (acid-base balance) in the blood.

Aging and Your Kidneys

With advancing age the kidneys shrink due to a loss of nephrons within the cortical region of the kidney. There is also evidence of collapsing of glomeruli and sclerotic changes in the larger renal blood vessels. The end result is a decrease in renal blood flow from a level of 1200 ml/min in young adults to 600 ml/min in people over the age of 80. This change in renal blood flow compromises our ability to eliminate unwanted substances from the blood stream. There is considerable variability in the population and many individuals have much loss of kidney function. But on average a linear decline in the GFR occurs after the age of 40. Other functions like glucose resorption are also decreased in the aged.

This decrease in GFR means that, for drugs excreted by the kidney, the doses of drugs need to be adjusted to compensate for the age-related decrease in renal function. If adjustments are not made, there is an age- http://www.usc.edu/dept/gero/AgeWorks/fall_session/dl/gero500/biology_a_lect/index_c.htm (2 of 6)10/3/07 11:20 PM Week 6: Cardiovascular, Respiratory and Urinary Systems

related risk for drug overdose. The risk for age-related drug complications is compounded further by age- related decreases in the liver metabolism of drugs.

The loss of nephrons also results in a decrease in the production of renin and secondarily, aldosterone. The decrease in aldosterone decreases potassium secretion by the nephron and can produce a condition known as hyperkalemia (potassium deficiency). Hyperkalemia is just one of many causes of hypertension in the elderly. This age-related problem can be further exacerbated by certain drugs (i.e. ibuprofen) which block the ability of aldosterone to help rid our blood stream of excess potassium.

This figure shows the difference in glomerular filtration rate (GFR) for a young and an old kidney. The process is based on two stages. First, the oxygenated blood flows in the kidney (the kidney is more RED). Secondly, as the larger particles are being taken out of the blood (the cup is filling up) and the deoxygenated blood (the kidney is more BLUE) is flowing out of the kidney. The older kidney has a lower concentration of the urine (lighter yellow with fewer particles in it).

Age-Related Disease in Your Kidneys

Glomerulonephritis: an inflammation of the basic kidney filtration units. Hypertension and edema are common and, in worse cases, protein and blood can be found in the urine. The treatment is with antibiotics for bacterial infections and steroids to reduce the inflammation.

Renal Artery Disease: Atherosclerotic changes are common in the renal arteries and can lead to acute and chronic renal failure when there is an occlusion of the renal artery (i.e. emboli or thrombi). Abdominal aortic aneurysms are often associated with occlusive disease. The best treatment is surgical repair (revascularization of the kidney).

Chronic Renal Failure: Atherosclerosis, diabetes, prostate problems (hypertrophy and cancer) and drug toxicity(especially digoxin) are just a few causes of chronic renal failure. The most common event in older persons is renal failure secondary to heart failure. The most common therapy for chronic renal failure is hemodialysis. Kidney transplants not common in older patients, but this has been changing in recent years.

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Lower Urinary Tract: Urine is stored in the urinary bladder and released through the voluntary control of two sphincters located between the urinary bladder and urethra. The internal sphincter responds to pressure resulting from bladder distention and the external sphincter is under voluntary control (brain). The release of the internal sphincter is considered reflexive, while the external is conscious. In the absence of control from the brain, spinal reflexes will take over and void urine whenever the bladder is distended.

Urinary incontinence: There are a number of age related changes which influence our ability to maintain continence. First, there are central nervous system determinants which include the cognitive ability to understand the need to remain continent (i.e., Alzheimer's disease) and there must be a motivation which can be altered in conditions such as severe depression. Second, the integrity of each of the muscles of the lower urinary tract are crucial. Weakening of the bladder or the sphincters can reduce one's ability to maintain continence. Third, a number of drugs can influence one's ability to retain urine in the bladder. Lastly, a number of disease conditions can cause incontinence (i.e. diabetes, UTI's). Urinary incontinence is the involuntary loss of urine and it is most frequently observed in the elderly.

Women: The primary cause for incontinence in women is menopause and the loss of estrogen. All of the tissue of the lower urinary tract and reproductive tracts are stimulated by estrogen to maintain their growth and function (referred to as a trophic influence). After menopause, the urinary bladder and sphincters weaken, urethral smooth muscle weakens, and atrophic vaginitis can occur - all of which decrease urethral pressure and contraction with aging. Therapies to alleviate incontinence include exercises to strengthen the pelvic muscles (Kegel's exercises, used during and after pregnancy) and estrogen supplementation therapy (Premarin & Provera).

Men: The most common cause of incontinence in men is prostatic hypertrophy where prostatic tissue compresses. Growth of the prostate inward toward the urethra reduces the passage of urine during voiding. Treatments include drugs that block the action of testosterone, the hormone that stimulates prostrate growth. When drug therapy doesn't alleviate symptoms, a simple surgical technique, called transurethral resection (TUR) of the Prostate, is usually done.

Something to Consider...

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Urinary Incontinence

This exercise requires you to answer three questions about the effects of urinary incontinence based on web sites provided and the lecture.

The data: Urinary incontinence is the second leading cause of institutionalization among the elderly. In the non-institutionalized, approximately 19% of men and 39% of women are urinary incontinent. For those in nursing homes, between 50% to 70% of the 1.5 million residents are incontinent.

The issues: 1. Based on your research from the web, what are the types of urinary incontinence? 2. What are some of the methods of treatment of urinary incontinence? 3. Is there typically a difference in etiology (cause) between men and women?

Suggested websites for information: (feel free to use any other sites):

The National Institute on Aging http://www.nih.gov/nia/

The International Society for Peritoneal Dialysis http://www.ispd.org

The National Association for Continence http://www.nafc.org/

Quiz #2

Chapter 10 - Opportunities and Stresses of Informal Caregiving

Please make sure you have read Chapter 10 in your text before you take the quiz.

Please take the following 10 item quiz. Once you have completed the quiz, follow the instructions to send me a copy of your results.

Thank You and Good Luck!

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Quiz Instructions:

[ Fill in the Blank ]

After you finish the quiz you will see your results. At the very bottom fill out the "Routing Information" section in order to send me a copy (And Be Honest!). Please send the results to [email protected] and choose "Send as: Text".

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