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NARRATIVE PATHOPHYSIOLOGY

NON MODIFIABLE FACTORS Age persons above 40 years of age are high risk in developing cardiovascular diseases because of degenerative changes in the heart and blood vessels Gender males are more prone to heart diseases before the age of 65. However, females have higher propensity to cardiovascular disorders after the age of 65 due to decreased estrogen levels in menopause. HDL (high density lipoprotein/good cholesterol) decreases, LDL (low density lipoprotein/bad cholesterol) increases and causes the development of atherosclerosis. Race In the US, cardiovascular diseases rank the number one cause of morbidity because of their diet, they dont eat much rice but more on food chains and soft drinks and fats. Genetics persons with family history of cardiovascular disorders are at risk to develop these diseases MODIFIABLE FACTORS Stress sympathetic response stimulation causes increased secretion of norepinephrine. This results to vasoconstriction and tachycardia. Increased BP and increased cardiac workload occur. Diet increased dietary intake of foods high in sodium, fats and cholesterol predisposes a person to cardiovascular disorders. Sodium retains water and increases blood volume. This may cause hypertension. High fats and high cholesterol diet predisposes a person to atherosclerosis. Exercise regular pattern of exercise improves circulation to different body parts including the heart and blood vessels; maintains vascular tone; and enhances release of chemical activators )tissue type of plasminogen activators), which prevent platelet aggregation and prevent blood clotting. Sedentary lifestyle increases risk to cardiovascular disorders. Cigarette smoking nicotine causes vasoconstriction and spasm of the arteries; increases myocardial oxygen demands; and adhesion of platelets. In addition, cigarette smoking has been associated with decreased levels of HDL. Also, more carbon dioxide is inhaled than oxygen. Alcohol it positively correlates with high blood pressure. Alcohol causes vasoconstriction. Thirty mls of alcohol is stimulant and causes vasodilation. More than 30mls of alcohol causes vasoconstriction and elevation of blood pressure. Hypertension increased systemic vascular resistance, endothelial damage, increased platelet adherence, and increased permeability of endothelial lining, result from elevated blood pressure

Hyperlipdemia hypercholesterolemia. Increased LDL cholesterol damages endothelium and causes accumulation of fatty plaques on endothelial lining and proliferation of smooth muscle cells. Diabetes Mellitus glucose from carbohydrates cannot be transported into the cells due to insulin deficiency or increased resistance to insulin. The body then, mobilizes fats (lipolysis), to become a source of glucose. However, not all of the fats converted into glucose. Most of it remains as lipids. Hyperlipidemia results, which enhances the risk of atherosclerosis. Obesity this results to increased cardiac workload. The heart has to pump blood supply to a larger body surface area. May also be characterized by rise in serum lipid levels. Contraceptive pills may precipitate thromboembolism and HPN. The estrogen component of oral contraceptive pills increases blood viscosity, thereby increasing the risk to thromboembolism. It also stimulates the liver to synthesize angiotensin. The angiotensinogen triggers production of pulmonary converting enzymes. This in turn causes conversion of angiotensinogen to Angiotensin I, a vasoconstrictor. Angiotensinogen I is further acted upon by pulmonary converting enzyme and converted to Angiotensin II, a very potent vasoconstrictor. And then leads now to elevated blood pressure. Atherosclerosis is patchy intimal plaques (atheromas) in medium-sized and large arteries; the plaques contain lipids, inflammatory cells, smooth muscle cells, and connective tissue. Risk factors include dyslipidemia, diabetes, cigarette smoking, family history, sedentary lifestyle, obesity, and hypertension. Symptoms develop when growth or rupture of the plaque reduces or obstructs blood flow; symptoms vary by artery affected. Diagnosis is clinical and confirmed by angiography, ultrasonography, or other imaging tests. Treatment includes risk factor and dietary modification, physical activity, antiplatelet drugs, and antiatherogenic drugs. The hallmark of atherosclerosis is the atherosclerotic plaque, which contains lipids (intracellular and extracellular cholesterol and phospholipids), inflammatory cells (eg, macrophages, T cells), smooth muscle cells, connective tissue (eg, collagen, glycosaminoglycans, elastic fibers), thrombi, and Ca deposits. All stages of atherosclerosisfrom initiation and growth to complication of the plaqueare considered an inflammatory response to injury. Endothelial injury is thought to have a primary role. ATHEROSCLEROSIS Atherosclerosis preferentially affects certain areas of the arterial tree. Nonlaminar or turbulent blood flow (eg, at branch points in the arterial tree) leads to endothelial dysfunction and inhibits endothelial production of nitric oxide, a potent vasodilator and anti-inflammatory molecule. Such blood flow also stimulates endothelial cells to produce adhesion molecules, which recruit and bind inflammatory cells. Risk factors for atherosclerosis (eg, dyslipidemia, diabetes, cigarette smoking, hypertension), oxidative stressors (eg, superoxide radicals), angiotensin II, and

systemic infection and inflammation also inhibit nitric oxide production and stimulate production of adhesion molecules, proinflammatory cytokines, chemotactic proteins, and vasoconstrictors; exact mechanisms are unknown. The net effect is endothelial binding of monocytes and T cells, migration of these cells to the subendothelial space, and initiation and perpetuation of a local vascular inflammatory response. Monocytes in the subendothelium transform into macrophages. Lipids in the blood, particularly low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), also bind to endothelial cells and are oxidized in the subendothelium. Uptake of oxidized lipids and macrophage transformation into lipid-laden foam cells result in the typical early atherosclerotic lesions called fatty streaks. Degraded erythrocyte membranes that result from rupture of vasa vasorum and intraplaque hemorrhage may be an important additional source of lipids within plaques. Macrophages elaborate proinflammatory cytokines that recruit smooth muscle cell migration from the media and that further attract and stimulate growth of macrophages. Various factors promote smooth muscle cell replication and increase production of dense extracellular matrix. The result is a subendothelial fibrous plaque with a fibrous cap, made of intimal smooth muscle cells surrounded by connective tissue and intracellular and extracellular lipids. A process similar to bone formation causes calcification within the plaque. Atherosclerotic plaques may be stable or unstable. Stable plaques regress, remain static, or grow slowly over several decades until they may cause stenosis or occlusion. Unstable plaques are vulnerable to spontaneous erosion, fissure, or rupture, causing acute thrombosis, occlusion, and infarction long before they cause stenosis. Most clinical events result from unstable plaques, which do not appear severe on angiography; thus, plaque stabilization may be a way to reduce morbidity and mortality. The strength of the fibrous cap and its resistance to rupture depend on the relative balance of collagen deposition and degradation. Plaque rupture involves secretion of metalloproteinases, cathepsins, and collagenases by activated macrophages in the plaque. These enzymes digest the fibrous cap, particularly at the edges, causing the cap to thin and ultimately rupture. T cells in the plaque contribute by secreting cytokines. Cytokines inhibit smooth muscle cells from synthesizing and depositing collagen, which normally reinforces the plaque. Once the plaque ruptures, plaque contents are exposed to circulating blood, triggering thrombosis; macrophages also stimulate thrombosis because they contain tissue factor, which promotes thrombin generation in vivo. One of 5 outcomes may occur: The resultant thrombus may organize and be incorporated into the plaque, changing the plaque's shape and causing its rapid growth. The thrombus may rapidly occlude the vascular lumen and precipitate an acute ischemic event. The thrombus may embolize. The plaque may fill with blood, balloon out, and immediately occlude the artery. Plaque contents (rather than thrombus) may embolize, occluding vessels downstream. Plaque stability depends on multiple factors,

including plaque composition (relative proportion of lipids, inflammatory cells, smooth muscle cells, connective tissue, and thrombus), wall stress (cap fatigue), size and location of the core, and configuration of the plaque in relation to blood flow. By contributing to rapid growth and lipid deposition, intraplaque hemorrhage may play an important role in transforming stable into unstable plaques. In general, unstable coronary artery plaques have a high macrophage content, a thick lipid core, and a thin fibrous cap; they narrow the vessel lumen by < 50% and tend to rupture unpredictably. Unstable carotid artery plaques have the same composition but typically cause problems through severe stenosis and occlusion or deposition of platelet thrombi, which embolize rather than rupture. Low-risk plaques have a thicker cap and contain fewer lipids; they often narrow the vessel lumen by > 50% and may produce predictable exercise-induced stable angina. Clinical consequences of plaque rupture in coronary arteries depend not only on plaque anatomy but also on relative balance of procoagulant and anticoagulant activity in the blood and on the vulnerability of the myocardium to arrhythmias. A link between infection and atherosclerosis has been observed, specifically an association between serologic evidence of certain infections (eg, Chlamydia pneumoniae, cytomegalovirus) and coronary artery disease (CAD). Putative mechanisms include indirect effects of chronic inflammation in the bloodstream, cross-reactive antibodies, and inflammatory effects of infectious pathogens on the arterial wall. CONGESTIVE HEART FAILURE The heart is fundamentally a blood pump. It pumps blood from the right side of the heart to the lungs to pick up oxygen. The oxygenated blood returns to the left side of the heart. The left side of the heart then pumps blood into the circulatory system of blood vessels that carry blood throughout the body. The heart consists of four chambers.

The two upper chambers are called atria and the two lower chambers are called ventricles. The right atrium and right ventricle receive blood from the body through the veins and then pump the blood to the lungs. The left atrium and left ventricle receive blood from the lungs and pump it out through the aorta into the arteries, which feed all organs and tissues of the body with oxygenated blood. Because the left ventricle has to pump blood to the entire body, it is a stronger pump than the right ventricle. Heart failure sounds frightening because it sounds like the heart just stops working. Do not be discouraged by the term heart failure. Heart failure means the tissues of the body are temporarily not receiving as much blood and oxygen as needed. With advancements in diagnosis and therapy for heart failure, patients are feeling better and living longer.

Picture of congestive heart failure. The heart is a pump that works together with the lungs. The heart pumps blood from the veins through the lungs where oxygen is added and then moves it on to the arteries. This pumping action creates a relatively high pressure in the arteries and a low pressure in the veins. Heart failure is an illness in which the pumping action of the heart becomes less and less powerful. When this happens, blood does not move efficiently through the circulatory system and starts to back up, increasing the pressure in the blood vessels and forcing fluid from the blood vessels into body tissues. Symptoms depend on which area of the body is most involved in the reduced pumping action.

When the left side of the heart (left ventricle) starts to fail, fluid collects in the lungs (pulmonary edema). This extra fluid in the lungs (pulmonary congestion) makes it more difficult for the airways to expand as a person inhales. Breathing becomes more difficult and the person may feel short of breath, particularly with activity or when lying down. When the right side of the heart (right ventricle) starts to fail, fluid begins to collect in the feet and lower legs. Puffy leg swelling (edema) is a sign of right heart failure, especially if the edema is pitting edema. With pitting edema, a finger pressed on the swollen leg leaves an imprint. Non-pitting edema is not caused by heart failure. As the right heart failure worsens, the upper legs swell and eventually the abdomen collects fluid (ascites). Weight gain accompanies the fluid retention and is a reliable measure of how much fluid is being retained. Although heart failure is a serious medical condition, there are many causes and the outcome can vary from person to person. Heart failure may develop gradually over several years, or more quickly after a heart attack or a disease of the heart muscle. Congestive heart failure (CHF) is generally classified as systolic or diastolic heart failure and becomes progressively more common with increasing age. In addition, patients with risk factors for heart disease are more likely to develop congestive heart failure. Systolic heart failure: This condition occurs when the pumping action of the heart is reduced or weakened. A common clinical measurement is ejection fraction (EF). The ejection fraction is a calculation of how much blood is ejected out of the left ventricle (stroke volume) divided by the maximum volume remaining in the left ventricle at the end of diastole, or when the heart is relaxed after filling with blood. A normal ejection fraction is greater than 55%. Systolic heart

failure is diagnosed when the ejection fraction has significantly decreased below the threshold of 55%. Diastolic heart failure: This condition occurs when the heart can contract normally but is stiff, or less compliant, when it is relaxing and filling with blood. The heart is unable to fill with blood properly, which produces backup into the lungs and heart failure symptoms. Diastolic heart failure is more common in patients older than 75 years of age, especially in patients with high blood pressure, and it is also more common in women. In diastolic heart failure, the ejection fraction is normal or increased. Congestive heart failure (CHF) is a syndrome that can be brought about by several causes. Congestive heart failure is a weakening of the heart caused by an underlying heart or blood vessel problem, or a combination of several different problems, including the following:

Weakened heart muscle (cardiomyopathy) Damaged heart valves Blocked blood vessels supplying the heart muscle (coronary arteries), which may lead to a heart attack (This is known as ischemic cardiomyopathy. If there are other, noncoronary causes, these are collectively termed nonischemic cardiomyopathy.) Toxic exposures, such as alcohol or cocaine Infections, commonly viruses, which for unknown reasons affect the heart in only certain individuals High blood pressure that results in thickening of the heart muscle (left ventricular hypertrophy) Congenital heart diseases Certain genetic diseases involving the heart Prolonged, serious arrhythmias A variety of less common disorders in which the heart muscle is infiltrated by a disease process There are over a hundred other less common causes of heart failure, which include a variety of infections, exposures (such as radiation orchemotherapy), endocrine disorders (including thyroid disorders), complications of other diseases, toxic effects, and genetic predisposition. However, the cause of congestive heart failure is often idiopathic, or unknown. People who have diabetes are at increased risk for both ischemic and nonischemic heart failure. Congestive heart failure may be exacerbated by the following lifestyle habits:

Unhealthy habits, such as smoking and excessive use of alcohol Obesity and lack of exercise (May contribute to congestive heart failure, either directly or indirectly through accompanying high blood pressure, diabetes, and coronary artery disease.) High salt intake, which may cause more fluid retention Noncompliance with medications and other therapies Whether through disease and/or complicating lifestyle choices, the pumping action of the heart can be impaired by several physiologic mechanisms:

Direct heart muscle damage (cardiomyopathy): The heart muscle can become weak because of damage or disease and thus does not contract or squeeze as forcefully as it should. This damage to the muscle can occur from any of the diseases mentioned above, but sometimes, the cause is unknown. Damage to heart muscle due to blockage: When the coronary blood supply is blocked, this results in a heart attack (myocardial infarction). A heart attack commonly causes severe pain in the chest, shortness of breath, nausea, sweating, and/or a feeling of impending doom. A heart attack may rapidly lead to either cardiac arrest (no heartbeat) or permanent damage to the left ventricle. If this damage is bad enough, that part of the heart will not work properly, which leads to heart failure. Prompt (emergency) medical attention is critical for all heart attacks. High blood pressure (hypertension): Abnormally high blood pressure increases the amount of work the left ventricle has to do to pump blood out to the circulatory system. Over time, this greater workload can damage and weaken the heart, leading to heart failure. Proper treatment of high blood pressure can prevent left ventricular failure. Heart valve problems: The valves of the heart normally keep the blood flowing in the proper direction through the heart. Abnormal heart valves impede this forward flow in one of two ways: o An incompetent valve is a valve that does not close properly when it should and allows blood to flow backward in the heart, "against the current." When blood flows the wrong way across a valve, the heart has to work harder to keep up its output. Eventually, this backed up blood accumulates in the lungs and the body and the heart muscle weakens. o A stenotic valve is a valve that does not open properly. Blood flow through the narrowed opening is blocked, creating an increased workload on the heart that can also lead to heart failure. Abnormal rhythm or irregular heartbeat: Abnormal heart rhythms can lower the heart's effectiveness as a pump. The rhythm may be too slow or too fast, or irregular. The heart has to pump harder to overcome these rhythm disorders. If this excessively slow or fast heartbeat is sustained over hours, days, or weeks, the heart can weaken, which may lead to heart failure. People with congestive heart failure sometimes do not suspect a problem with their heart or have symptoms that may not obviously be from the heart.

Early symptoms may include shortness of breath, cough, or a feeling of not being able to get a deep breath, especially when lying down. If a person has a known breathing problem, such as asthma, chronic obstructive pulmonary disease (COPD), oremphysema, they may they are having an "attack" or worsening of that condition. If a person usually does not have breathing problems, they may think they have a cold,flu, or bronchitis. Any or several of these above conditions may coexist along with congestive heart failure.

Congestive heart failure can have the following major symptoms:

Exercise intolerance o A person may be unable to tolerate exercise or even mild physical exertion that he or she may have been able to do before. The body needs oxygen and other nutrients during physical activity. A failing heart cannot pump enough blood to provide these nutrients to the body. o The ability to exercise, or even to walk at a normal pace, may be limited by feeling tired (fatigue) and having shortness of breath. Shortness of breath o If a person has congestive heart failure, he or she may have difficulty breathing (dyspnea), especially when he or she is active. Ordinary activities, such as sweeping or even walking around the house, may be difficult or impossible. The shortness of breath that accompanies these activities usually gets better with rest. o When congestive heart failure worsens, fluid backs up into the lungs and interferes with oxygen getting into the blood, causing dyspnea at rest and at night (orthopnea). If a person has congestive heart failure, he or she may awaken at night short of breath and have to sit or stand up to get relief. This condition is known as paroxysmal nocturnal dyspnea. Several pillows may help with a more comfortable sleep. A person may also prefer sleeping in a recliner rather than in a bed. As the buildup of fluid in the lungs becomes very severe, a frothy, pink liquid may be coughed up. Fluid retention and swelling o Puffy swelling (edema) in the legs, the feet, and the ankles may occur, particularly at the end of the day or after prolonged sitting. Often, the swelling is more noticeable in the ankles or on the lower leg in the front where the bone, the tibia, is close to the skin. o Pitting edema can occur when pressing down on the skin in the puffy areas. The indentation where the finger pressed may be visible for a few minutes. Pitting edema is not synonymous with heart failure; it can have other causes, including liver and kidney failure. Nonpitting edema is generally not caused by heart failure. o Swelling may be so severe as to reach up to the hips, scrotum, abdominal wall, and eventually, the abdominal cavity (ascites). o Daily weight checks are necessary in persons with heart failure because the amount of fluid retention is usually reflected by the amount of weight gain and increasing shortness of breath. Persons with heart failure should know their dry weight, which is what they weigh when they feel good with no pitting edema. Once a diagnosis of heart failure is established, evaluation of heart failure is important. Providing a complete and accurate history of symptoms is essential. Two major groups have established various stages of congestive heart failure. The American College of Cardiology/American Heart Association stages patients according to the progression of their heart failure. The stages are as follows:

Stage A: High risk for developing heart failure o Patient has one or more risk factors for developing heart failure. Stage B: Asymptomatic heart failure

This stage includes patients who have an enlarged or dysfunctional left ventricle from any cause, but are asymptomatic. Stage C: Symptomatic heart failure o Patient experiences heart failure symptoms -- shortness of breath, fatigue, inability to exercise, etc. (The patient is classified as Stage C) Stage D: Refractory end-stage heart failure o Patient has heart failure symptoms at rest in spite of medical treatment. o Cardiac transplantation, mechanical devices, more aggressive medical therapy, or end-oflife care may be necessary. The New York Heart Association classifies patients based on their physical limitations. Classifications are as follows:

Class I: No limitations of physical activity, no symptoms with ordinary activities Class II: Slight limitation, symptoms with ordinary activities Class III: Marked limitation, symptoms with less than ordinary activities Class IV: Severe limitation, symptoms of heart failure at rest (The patient is classified as Class IV) DIABETES MELLITUS TYPE II Diabetes mellitus (DM) is a set of related diseases in which the body cannot regulate the amount of sugar (specifically, glucose) in the blood. The blood delivers glucose to provide the body with energy to perform all of a person's daily activities.

The liver converts the food a person eats into glucose. The glucose is then released into the bloodstream. In a healthy person, the blood glucose level is regulated by several hormones, primarliy insulin. Insulin is produced by the pancreas, a small organ between the stomach and liver. The pancreas also makes other important enzymes released directly into the gut that helps digest food. Insulin allows glucose to move out of the blood into cells throughout the body where it is used for fuel. People with diabetes either do not produce enough insulin (type 1 diabetes) or cannot use insulin properly (type 2 diabetes), or both (which occurs with several forms of diabetes). In diabetes, glucose in the blood cannot move efficiently into cells, so blood glucose levels remain high. This not only starves all the cells that need the glucose for fuel, but also harms certain organs and tissues exposed to the high glucose levels. Type 2 diabetes (T2D): Although the pancreas still secretes insulin, the body of someone with type 2 diabetes is partially or completely unable to use this insulin. This is sometimes referred to as insulin resistance. The pancreas tries to overcome this resistance by secreting more and more insulin. People with insulin resistance develop type 2 diabetes when they fail to secrete enough insulin to cope with their higher demands.

At least 90% of adult individuals with diabetes have type 2 diabetes. Type 2 diabetes is typically diagnosed in adulthood, usually after age 45 years. It used to be called adult-onset diabetes mellitus, or non-insulin-dependent diabetes mellitus. These names are no longer used because type 2 diabetes does occur in younger people, and some people with type 2 diabetes require insulin therapy. Type 2 diabetes is usually controlled with diet, weight loss, exercise, and oral medications. However, more than half of all people with type 2 diabetes require insulin to control their blood sugar levels at some point in the course of their illness. Complications of diabetes Both type 1 and type 2 diabetes ultimately lead to high blood sugar levels, a condition called hyperglycemia. Over a long period of time, hyperglycemia damages the retina of the eye, the blood vessels of the kidneys, the nerves, and other blood vessels.

Damage to the retina from diabetes (diabetic retinopathy) is a leading cause of blindness. Damage to the kidneys from diabetes (diabetic nephropathy) is a leading cause of kidney failure. Damage to the nerves from diabetes (diabetic neuropathy) is a leading cause of foot wounds and ulcers, which frequently lead to foot and leg amputations. Damage to the nerves in the autonomic nervous system can lead to paralysis of the stomach (gastroparesis), chronic diarrhea, and an inability to control heart rate and blood pressure during postural changes. Diabetes accelerates atherosclerosis, (the formation of fatty plaques inside the arteries), which can lead to blockages or a clot (thrombus). Such changes can then lead to heart attack, stroke, and decreased circulation in the arms and legs (peripheral vascular disease). Diabetes predisposes people to elevated blood pressure, high levels of cholesterol and triglycerides. These conditions both independently and together with hyperglycemia, increase the risk of heart disease, kidney disease, and other blood vessel complications. Diabetes can contribute to a number of acute (short-lived) medical problems.

Many infections are associated with diabetes, and infections are frequently more dangerous in someone with diabetes because the body's normal ability to fight infections is impaired. To compound the problem, infections may worsen glucose control, which further delays recovery from infection. Hypoglycemia or low blood sugar, occurs intermittently in most people with diabetes. It can result from taking too much diabetes medication or insulin (sometimes called an insulin reaction), missing a meal, exercising more than usual, drinking too much alcohol, or taking certain medications for other conditions. It is very important to recognize hypoglycemia and be prepared to treat it at all times. Headache, feeling dizzy, poor concentration, tremor of the hands, and sweating are common symptoms of hypoglycemia. A person can faint or have a seizure if blood sugar level become too low. Diabetic ketoacidosis (DKA) is a serious condition in which uncontrolled hyperglycemia (usually due to complete lack of insulin or a relative deficiency of insulin) over time creates a buildup of ketones (acidic waste products ) in the blood. High levels of ketones can be very harmful. This typically happens to people with type 1 diabetes who do not have good blood

glucose control. Diabetic ketoacidosis can be precipitated by infection, stress, trauma, missing medications like insulin, or medical emergencies such as a stroke and heart attack. Hyperosmolar hyperglycemic nonketotic syndrome is a serious condition in which the blood sugar level gets very high. The body tries to get rid of the excess blood sugar by eliminating it in the urine. This increases the amount of urine significantly, and often leads to dehydration so severe that it can cause seizures, coma, and even death. This syndrome typically occurs in people with type 2 diabetes who are not controlling their blood sugar levels, who have become dehydrated, or who have stress, injury, stroke, or are taking certain medications, like steroids. Symptoms of type 2 diabetes are often subtle and may be attributed to aging or obesity.

A person may have type 2 diabetes for many years without knowing it. People with type 2 diabetes can develop hyperglycemic hyperosmolar nonketotic syndrome. Type 2 diabetes can be precipitated by steroids and stress. If not properly treated, type 2 diabetes can lead to complications such as blindness,kidney failure, heart disease, and nerve damage. Common symptoms of both type 1 and type 2 diabetes include:

Fatigue, constantly tired: In diabetes, the body is inefficient and sometimes unable to use glucose for fuel. The body switches over to metabolizing fat, partially or completely, as a fuel source. This process requires the body to use more energy. The end result is feeling fatigued or constantly tired. Unexplained weight loss: People with diabetes are unable to process many of the calories in the foods they eat. Thus, they may lose weight even though they eat an apparently appropriate or even an excessive amount of food. Losing sugar and water in the urine and the accompanying dehydration also contributes to weight loss. Excessive thirst (polydipsia): A person with diabetes develops high blood sugar levels, which overwhelms the kidney's ability to reabsorb the sugar as the blood is filtered to make urine. Excessive urine is made as the kidney spills the excess sugar. The body tries to counteract this by sending a signal to the brain to dilute the blood, which translates into thirst. The body encourages more water consumption to dilute the high blood sugar back to normal levels and to compensate for the water lost by excessive urination. Excessive urination (polyuria): Another way the body tries to rid the body of the extra sugar in the blood is to excrete it in the urine. This can also lead to dehydration because a large amount of water is necessary to excrete the sugar. Excessive eating (polyphagia): If the body is able, it will secrete more insulin in order to try to manage the excessive blood sugar levels. Moreover, the body is resistant to the action of insulin in type 2 diabetes. One of the functions of insulin is to stimulate hunger. Therefore, higher insulin levels lead to increased hunger. Despite increased caloric intake, the person may gain very little weight and may even lose weight. Poor wound healing: High blood sugar levels prevent white blood cells, which are important in defending the body against bacteria and also in cleaning up dead tissue and cells, from functioning normally. When these cells do not function properly, wounds take much longer to heal and become infected more frequently. Long-standing diabetes also is associated with

thickening of blood vessels, which prevents good circulation, including the delivery of enough oxygen and other nutrients to body tissues. Infections: Certain infections, such as frequent yeast infections of the genitals, skin infections, and frequent urinary tract infections, may result from suppression of the immune system by diabetes and by the presence of glucose in the tissues, which allows bacteria to grow. These infections can also be an indicator of poor blood sugar control in a person known to have diabetes. Altered mental status: Agitation, unexplained irritability, inattention, extreme lethargy, or confusion can all be signs of very high blood sugar, ketoacidosis, hyperosmolar hyperglycemia nonketotic syndrome, or hypoglycemia (low sugar). Thus, any of these merit the immediate attention of a medical professional. Blurry vision: Blurry vision is not specific for diabetes but is frequently present with high blood sugar levels. COMPLICATIONS OF DM Diabetes mellitus (DM), both type 1 and type 2, affects many organ systems, particularly the heart, eyes, kidneys, and the peripheral and autonomic nervous systems. Also, macrosomia and birth complications occur more often in infants born to women with inadequately controlled diabetes mellitus. Prevention of macrovascular complications depends on control of the major risk factors for cardiac disease, such as smoking, blood pressure, and blood lipid concentrations; blood glucose control has been less effective in controlled trials. For prevention of microvascular damage, glycemic control is essential, and control of blood pressure and other vascular parameters is also important. DIABETIC NEPHROPATHY Diabetic nephropathy involves pathologic changes to the kidney vasculature. If uncontrolled, the disease progresses from microalbuminuria to macroalbuminuria and an elevated plasma creatinine concentration, and eventually to endstage disease requiring dialysis or transplant. Pathogenesis involves hypertension, ischemia, hyperglycemia, and advanced glycosylation end products. Persistently elevated blood glucose, blood pressure, and cholesterol and triglyceride concentrations are associated with microalbuminuria. Microalbuminuria, defined as a persistent loss of albumin in the urine of 30 to 299 mg/day, is the first indication of nephropathy. Macroalbuminuria is diagnosed when urinary albumin losses are 300 mg/day. A random urine specimen with an albumin concentration of greater than 30 mg/L suggests microalbuminuria. Falsenegative or falsepositive results may occur due to urine volume at time of collection. A urine albumin/creatinine ratio with a value of 30 g/mg or greater also suggests microalbuminuria.

Transient microalbuminuria may occur with hyperglycemia, exercise, heart failure, and febrile illness. When screening suggests microalbuminuria, a repeat specimen (albumin/creatinine ratio) should be obtained after waiting at least 1 to 2 weeks. A standard urine test strip can usually detect macroalbuminuria (1+ or greater). Albuminspecific test strips can detect microalbuminuria. However, falsenegatives and falsepositives are possible when using test strips. Twentyfour hour urine samples are not required to make these diagnoses. NEUROPATHY Neuropathy is a particularly common diabetes complication, affecting approximately half of all diabetes patients. Distal symmetric polyneuropathy is the most common presentation. However, neuropathy can also involve the autonomic nervous system and individual nerves. The disease may present with sensory loss, but also with paresthesia and dysesthesia in the affected areas. Pathogenesis may occur due to ischemia and metabolic factors, including advanced glycosylation end products. Progression is likely. If severe, neuropathy may lead to joint deformities and infections that ultimately require amputation. CARDIAC COMPLICATIONS Cardiovascular disease (CVD) is the leading cause of mortality in individuals with diabetes. Morbidity due to CVD is also common. Control of cardiac risk factors is therefore critical. These include smoking, hypertension, and hyperlipidemia and then leading to atherosclerosis. CHRONIC KIDNEY DISEASE Chronic kidney disease occurs when one suffers from gradual and usually permanent loss of kidney function over time. This happens gradually, usually over months to years. Chronic kidney disease is divided into five stages of increasing severity (see Table 1 below). The term "renal" refers to the kidney, so another name for kidney failure is "renal failure." Mild kidney disease is often called renal insufficiency. With loss of kidney function, there is an accumulation of water, waste, and toxic substances in the body that are normally excreted by the kidney. Loss of kidney function also causes other problems such as anemia, high blood pressure, acidosis (excessive acidity of body fluids), disorders of cholesterol and fatty acids, and bone disease. Stage 5 chronic kidney disease is also referred to as kidney failure, end-stage kidney disease, or end-stage renal disease, wherein there is total or near-total loss of kidney function. There is dangerous accumulation of water, waste, and toxic substances, and most individuals in this stage of kidney disease need dialysis or transplantation to stay alive. Unlike chronic kidney disease, acute kidney failure develops rapidly, over days or weeks.

Acute kidney failure usually develops in response to a disorder that directly affects the kidney, its blood supply, or urine flow from it. Acute kidney failure is often reversible, with complete recovery of kidney function. Some patients are left with residual damage and can have a progressive decline in kidney function in the future. Others may develop irreversible kidney failure after an acute injury and remain dialysisdependent.

Table 1. Stages of Chronic Kidney Disease GFR* mL/min/1.73 m2

Stage Description

Slight kidney damage with normal or More than 90 increased filtration Mild decrease in kidney function Moderate decrease in kidney function Severe decrease in kidney function Kidney failure 60 to 89 30 to 59 15 to 29 Less than 15 (or dialysis)

2 3 4 5

*GFR is glomerular filtration rate, a measure of the kidney

The kidneys are remarkable in their ability to compensate for problems in their function. That is why chronic kidney disease may progress without symptoms for a long time until only very minimal kidney function is left. Because the kidneys perform so many functions for the body, kidney disease can affect the body in a large number of different ways. Symptoms vary greatly. Several different body systems may be affected. Notably, most patients have no decrease in urine output even with very advanced chronic kidney disease.

Effects and symptoms of chronic kidney disease include:


need to urinate frequently, especially at night (nocturia); swelling of the legs and puffiness around the eyes (fluid retention); high blood pressure; fatigue and weakness (from anemia or accumulation of waste products in the body); loss of appetite, nausea and vomiting; itching, easy bruising, and pale skin (from anemia); shortness of breath from fluid accumulation in the lungs; headaches, numbness in the feet or hands (peripheral neuropathy), disturbed sleep, altered mental status (encephalopathy from the accumulation of waste products or uremic poisons), and restless legs syndrome; chest pain due to pericarditis (inflammation around the heart); bleeding (due to poor blood clotting); bone pain and fractures; and decreased sexual interest and erectile dysfunction. PLEURAL EFFUSION A pleural effusion is not normal. It is not a disease but rather a complication of an underlying illness. Extra fluid (effusion) can occur for a variety of reasons. Common classification systems divide pleural effusions based on the chemistry composition of the fluid and what causes the effusion to be formed. Two classifications are 1) transudate pleural effusions; and 2) exudate pleural effusions. Sometimes the pleural effusion can have characteristics of both a transudate and an exudate. 1. Transudate pleural effusions are formed when fluid leaks from blood vessels into the pleural space. Chemically, transudate pleural effusions contain less protein and LDH (lactate dehydrogenase) than exudate pleural effusions. If both the pleural fluidtoserum total protein ratio is less than or equal to 0.50 and the pleural fluidtoserum LDH ratios are less than or equal to 0.67, the fluid is usually considered to be a transudate while exudates ratios are above 0.50 and above 0.67. Examples of transudate pleural effusions include:

congestive heart failure, liver failure or cirrhosis, kidney failure or nephritic syndrome, and peritoneal dialysis.

2. Exudate pleural effusions are caused by inflammation of the pleura itself and are often due to disease of the lung. Examples of exudate causes include:

lung or breast cancer, lymphoma, pneumonia, tuberculosis, post pericardotomy syndrome, systemic lupus erythematosus, uremia or kidney failure, Meigs syndrome, pancreatic pseudocyst, ascites, Intra-abdominal abscess, and Asbestosis and mesothelioma.

Most pleural effusions are caused by congestive heart failure, pneumonia, pulmonary embolism and malignancy. Symptoms of Pleural includes: Shortness of breath is the most common symptom of a pleural effusion. As the effusion grows larger with more fluid, the harder it is for the lung to expand and the more difficult it is for the patient to breathe. Chest pain occurs because the pleural lining of the lung is irritated. The pain is usually described as pleuritic, defined as a sharp pain, worsening with a deep breath. While the pain may be localized to the chest, if the effusion causes inflammation of the diaphragm (the muscle that divides the chest from the abdominal cavity) the pain may be referred to the shoulder or the upper abdomen. As the pleural effusion increases in size, the pain may increase.

Other associated symptoms are due to the underlying disease. For example, individuals with:

congestive heart failure may complain of swelling of their feet and shortness of breath when lying flat, (orthopnea) or wakening them in the middle of the night (paroxysmal nocturnal dyspnea); tuberculosis may be have night sweats, cough up blood (hemoptysis), and lose weight; hemoptysis may have associated infection and lung cancer; pneumonia may complain of fever, shaking chills, cough producing colored sputum and pleuritic pain.

PNEUMONIA Pneumonia is an infection of one or both lungs which is usually caused by bacteria, viruses, or fungi. Prior to the discovery of antibiotics, one-third of all people who developed pneumonia subsequently died from the infection. Currently, over 3 million people develop pneumonia each year in the United States. Over a half a million of these people are admitted to a hospital for treatment. Although most of these people recover, approximately 5% will die from pneumonia. Symptoms include: Most people who develop pneumonia initially have symptoms of a cold (upper respiratory infection, for example, sneezing,sore throat, cough), which are then followed by a high fever (sometimes as high as 104 F), shaking chills, and a cough with sputum production. The sputum is usually discolored and sometimes bloody. Depending on the location of the infection, certain symptoms are more likely to develop. When the infection settles in the air passages, cough and sputum tend to predominate the symptoms. In some, the spongy tissue of the lungs that contain the air sacs is more involved. In this case, oxygenation of the blood can be impaired, along with stiffening of the lung, which results in shortness of breath. At times, the individual's skin color may change and become dusky or purplish (a condition known as "cyanosis") due to their blood being poorly oxygenated. The only pain fibers in the lung are on the surface of the lung, in the area known as the pleura. Chest pain may develop if the outer aspects of the lung close to the pleura are involved in the infection. This pain is usually sharp and worsens when taking a deep breath and is known as pleuritic pain orpleurisy. In other cases of pneumonia, depending on the causative organism, there can be a slow onset of symptoms. A worsening cough, headaches, and muscle aches may be the only symptoms. Children and babies who develop pneumonia often do not have any specific signs of a chest infection but develop a fever, appear quite ill, and can become lethargic. Elderly people may also have few symptoms with pneumonia.