Cardiovascular, Respiratory and Urinary Systems

Part I: The Cardiovascular System

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.

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.

   
   
   

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)

   
   
   

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.

   
   
   

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.

   
   
   

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
   
   
   

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.

   
   
   

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.
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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.