Anemia of Inflammation and Chronic Disease

What is anemia?

Anemia is a condition in which the blood has a lower-than-normal number of red blood cells (RBCs). RBCs contain hemoglobin, an iron-rich protein that gives blood its red color and allows RBCs to transport oxygen from the lungs to the tissues of the body. Because RBC numbers are low in anemia, blood hemoglobin levels are also low.

People with anemia may feel tired because their blood does not supply enough oxygen to the body’s organs and tissues. If anemia becomes severe and prolonged, the lack of oxygen in the blood can lead to shortness of breath or exercise intolerance—a condition in which a person becomes easily fatigued during or after physical activity—and eventually cause the heart and other organs to fail.

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What is anemia of inflammation and chronic disease (AI/ACD)?

AI/ACD is a type of anemia that commonly occurs with chronic, or long-term, illnesses or infections. Cancer and inflammatory disorders, in which abnormal activation of the immune system occurs, can also cause AI/ACD. Some people develop AI/ACD without having any signs of these health problems.

AI/ACD is easily confused with iron-deficiency anemia because in both forms of anemia, levels of iron circulating in the blood are low. Circulating iron is necessary for RBC production. Low blood iron levels occur in iron-deficiency anemia because levels of iron stored in the body’s tissues are depleted. In AI/ACD, however, iron stores are normal or high. Low blood levels occur in AI/ACD, despite normal iron stores, because inflammatory and chronic diseases interfere with the body’s ability to use stored iron and absorb iron from the diet. Certain treatments for chronic diseases may also impair RBC production and contribute to AI/ACD. AI/ACD is the second most common form of anemia, after iron-deficiency anemia, but it is rarely severe.

While AI/ACD can affect people at any age, older adults are especially susceptible because they have the highest rates of chronic disease. AI/ACD is also common among hospitalized patients, particularly those with chronic illnesses.

More than 130 million Americans live with chronic conditions.¹ Addressing the causes of anemia in people with chronic conditions can help improve their health and quality of life.

¹Chronic disease overview. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/nccdphp/overview.htm. Updated March 20, 2008. Accessed April 1, 2008.

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What causes AI/ACD?

A number of chronic diseases can cause anemia for different reasons.

Infectious and inflammatory diseases. As part of the immune response that occurs with infection and noninfectious inflammatory diseases, cells of the immune system release proteins called cytokines. These proteins help heal and defend the body against infection. But they can also affect normal body functions. In AI/ACD, immune cytokines interfere with the body’s ability to absorb and use iron. Cytokines may also interfere with the production and normal activity of erythropoietin (EPO), a hormone made by the kidneys that stimulates bone marrow to produce RBCs.

Infectious diseases that cause AI/ACD include tuberculosis, HIV, endocarditis—infection in the heart—and osteomyelitis, a bone infection. Sometimes acute infections—those that develop quickly and may not last long—can also cause AI/ACD.

Inflammatory diseases that can lead to AI/ACD include rheumatoid arthritis, lupus, diabetes, heart failure, degenerative joint disease, and inflammatory bowel disease (IBD). IBD, including Crohn’s disease, can also cause iron deficiency due to poor absorption of iron by the diseased intestine and bleeding from the gastrointestinal tract.

Kidney disease. People with kidney disease can develop anemia for several different reasons. For one, diseased kidneys often fail to make enough EPO. In addition, kidney disease results in abnormal absorption and use of iron, which is typical of AI/ACD. Because anemia worsens as kidney disease advances, nearly everyone with end-stage kidney disease has anemia.

People with kidney failure can also develop iron deficiency due to blood loss during hemodialysis, a procedure that removes blood from an artery, purifies it, and returns it to a vein, thereby doing the job that the kidneys no longer can. Low levels of iron and of folic acid—another nutrient required for normal RBC production—may also contribute to anemia in people with kidney disease.

Cancer. AI/ACD can occur with certain types of cancer, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and breast cancer. Like chronic inflammatory disorders and infections, these types of cancer cause inflammatory cytokines to be released in the body. The anemia of AI/ACD can also be made worse by cancer chemotherapy and radiation treatments that damage the bone marrow—where RBCs are produced—and by the cancer’s invasion of bone marrow.

Anemia of Inflammation and Chronic Disease

What is anemia?

Anemia is a condition in which the blood has a lower-than-normal number of red blood cells (RBCs). RBCs contain hemoglobin, an iron-rich protein that gives blood its red color and allows RBCs to transport oxygen from the lungs to the tissues of the body. Because RBC numbers are low in anemia, blood hemoglobin levels are also low.

People with anemia may feel tired because their blood does not supply enough oxygen to the body’s organs and tissues. If anemia becomes severe and prolonged, the lack of oxygen in the blood can lead to shortness of breath or exercise intolerance—a condition in which a person becomes easily fatigued during or after physical activity—and eventually cause the heart and other organs to fail.

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What is anemia of inflammation and chronic disease (AI/ACD)?

AI/ACD is a type of anemia that commonly occurs with chronic, or long-term, illnesses or infections. Cancer and inflammatory disorders, in which abnormal activation of the immune system occurs, can also cause AI/ACD. Some people develop AI/ACD without having any signs of these health problems.

AI/ACD is easily confused with iron-deficiency anemia because in both forms of anemia, levels of iron circulating in the blood are low. Circulating iron is necessary for RBC production. Low blood iron levels occur in iron-deficiency anemia because levels of iron stored in the body’s tissues are depleted. In AI/ACD, however, iron stores are normal or high. Low blood levels occur in AI/ACD, despite normal iron stores, because inflammatory and chronic diseases interfere with the body’s ability to use stored iron and absorb iron from the diet. Certain treatments for chronic diseases may also impair RBC production and contribute to AI/ACD. AI/ACD is the second most common form of anemia, after iron-deficiency anemia, but it is rarely severe.

While AI/ACD can affect people at any age, older adults are especially susceptible because they have the highest rates of chronic disease. AI/ACD is also common among hospitalized patients, particularly those with chronic illnesses.

More than 130 million Americans live with chronic conditions.¹ Addressing the causes of anemia in people with chronic conditions can help improve their health and quality of life.

¹Chronic disease overview. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/nccdphp/overview.htm. Updated March 20, 2008. Accessed April 1, 2008.

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What causes AI/ACD?

A number of chronic diseases can cause anemia for different reasons.

Infectious and inflammatory diseases. As part of the immune response that occurs with infection and noninfectious inflammatory diseases, cells of the immune system release proteins called cytokines. These proteins help heal and defend the body against infection. But they can also affect normal body functions. In AI/ACD, immune cytokines interfere with the body’s ability to absorb and use iron. Cytokines may also interfere with the production and normal activity of erythropoietin (EPO), a hormone made by the kidneys that stimulates bone marrow to produce RBCs.

Infectious diseases that cause AI/ACD include tuberculosis, HIV, endocarditis—infection in the heart—and osteomyelitis, a bone infection. Sometimes acute infections—those that develop quickly and may not last long—can also cause AI/ACD.

Inflammatory diseases that can lead to AI/ACD include rheumatoid arthritis, lupus, diabetes, heart failure, degenerative joint disease, and inflammatory bowel disease (IBD). IBD, including Crohn’s disease, can also cause iron deficiency due to poor absorption of iron by the diseased intestine and bleeding from the gastrointestinal tract.

Kidney disease. People with kidney disease can develop anemia for several different reasons. For one, diseased kidneys often fail to make enough EPO. In addition, kidney disease results in abnormal absorption and use of iron, which is typical of AI/ACD. Because anemia worsens as kidney disease advances, nearly everyone with end-stage kidney disease has anemia.

People with kidney failure can also develop iron deficiency due to blood loss during hemodialysis, a procedure that removes blood from an artery, purifies it, and returns it to a vein, thereby doing the job that the kidneys no longer can. Low levels of iron and of folic acid—another nutrient required for normal RBC production—may also contribute to anemia in people with kidney disease.

Cancer. AI/ACD can occur with certain types of cancer, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and breast cancer. Like chronic inflammatory disorders and infections, these types of cancer cause inflammatory cytokines to be released in the body. The anemia of AI/ACD can also be made worse by cancer chemotherapy and radiation treatments that damage the bone marrow—where RBCs are produced—and by the cancer’s invasion of bone marrow.

Your Urinary System and How It Works

The organs, tubes, muscles, and nerves that work together to create, store, and carry urine are the urinary system. The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the urethra.

How does the urinary system work?

Front view of urinary tract.

Your body takes nutrients from food and uses them to maintain all bodily functions including energy and self-repair. After your body has taken what it needs from the food, waste products are left behind in the blood and in the bowel. The urinary system works with the lungs, skin, and intestines—all of which also excrete wastes—to keep the chemicals and water in your body balanced. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing. Certain types of medications can also affect the amount of urine eliminated.

The urinary system removes a type of waste called urea from your blood. Urea is produced when foods containing protein, such as meat, poultry, and certain vegetables, are broken down in the body. Urea is carried in the bloodstream to the kidneys.

The kidneys are bean-shaped organs about the size of your fists. They are near the middle of the back, just below the rib cage. The kidneys remove urea from the blood through tiny filtering units called nephrons. Each nephron consists of a ball formed of small blood capillaries, called a glomerulus, and a small tube called a renal tubule. Urea, together with water and other waste substances, forms the urine as it passes through the nephrons and down the renal tubules of the kidney.

From the kidneys, urine travels down two thin tubes called ureters to the bladder. The ureters are about 8 to 10 inches long. Muscles in the ureter walls constantly tighten and relax to force urine downward away from the kidneys. If urine is allowed to stand still, or back up, a kidney infection can develop. Small amounts of urine are emptied into the bladder from the ureters about every 10 to 15 seconds.

The bladder is a hollow muscular organ shaped like a balloon. It sits in your pelvis and is held in place by ligaments attached to other organs and the pelvic bones. The bladder stores urine until you are ready to go to the bathroom to empty it. It swells into a round shape when it is full and gets smaller when empty. If the urinary system is healthy, the bladder can hold up to 16 ounces (2 cups) of urine comfortably for 2 to 5 hours.

Circular muscles called sphincters help keep urine from leaking. The sphincter muscles close tightly like a rubber band around the opening of the bladder into the urethra, the tube that allows urine to pass outside the body.

Nerves in the bladder tell you when it is time to urinate, or empty your bladder. As the bladder first fills with urine, you may notice a feeling that you need to urinate. The sensation to urinate becomes stronger as the bladder continues to fill and reaches its limit. At that point, nerves from the bladder send a message to the brain that the bladder is full, and your urge to empty your bladder intensifies.

When you urinate, the brain signals the bladder muscles to tighten, squeezing urine out of the bladder. At the same time, the brain signals the sphincter muscles to relax. As these muscles relax, urine exits the bladder through the urethra. When all the signals occur in the correct order, normal urination occurs.

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What causes problems in the urinary system?

Problems in the urinary system can be caused by aging, illness, or injury. As you get older, changes in the kidneys’ structure cause them to lose some of their ability to remove wastes from the blood. Also, the muscles in your ureters, bladder, and urethra tend to lose some of their strength. You may have more urinary infections because the bladder muscles do not tighten enough to empty your bladder completely. A decrease in strength of muscles of the sphincters and the pelvis can also cause incontinence, the unwanted leakage of urine. Illness or injury can also prevent the kidneys from filtering the blood completely or block the passage of urine.

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How are problems in the urinary system detected?

Urinalysis is a test that studies the content of urine for abnormal substances such as protein or signs of infection. This test involves urinating into a special container and leaving the sample to be studied.

Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through the urethra. Your doctor may want to do a urodynamic test if you are having symptoms that suggest problems with the muscles or nerves of your lower urinary system and pelvis—ureters, bladder, urethra, and sphincter muscles.

Urodynamic tests measure the contraction of the bladder muscle as it fills and empties. The test is done by inserting a small tube called a catheter through your urethra into your bladder to fill it either with water or a gas. Another small tube is inserted into your rectum or vagina to measure the pressure put on your bladder when you strain or cough. Other bladder tests use x-ray dye instead of water so that x-ray pictures can be taken when the bladder fills and empties to detect any abnormalities in the shape and function of the bladder. These tests take about an hour.

The Kidneys and How They Work

What do the kidneys do?

The kidneys are bean-shaped organs, each about the size of a fist. They are located near the middle of the back, just below the rib cage, one on each side of the spine. The kidneys are sophisticated reprocessing machines. Every day, a person’s kidneys process about 200 quarts of blood to sift out about 2 quarts of waste products and extra water. The wastes and extra water become urine, which flows to the bladder through tubes called ureters. The bladder stores urine until releasing it through urination.

The kidneys remove wastes and water from the blood to form urine. Urine flows from the kidneys to the bladder through the ureters.

Wastes in the blood come from the normal breakdown of active tissues, such as muscles, and from food. The body uses food for energy and self-repairs. After the body has taken what it needs from food, wastes are sent to the blood. If the kidneys did not remove them, these wastes would build up in the blood and damage the body.

The actual removal of wastes occurs in tiny units inside the kidneys called nephrons. Each kidney has about a million nephrons. In the nephron, a glomerulus—which is a tiny blood vessel, or capillary—intertwines with a tiny urine-collecting tube called a tubule. The glomerulus acts as a filtering unit, or sieve, and keeps normal proteins and cells in the bloodstream, allowing extra fluid and wastes to pass through. A complicated chemical exchange takes place, as waste materials and water leave the blood and enter the urinary system.

In the nephron (left), tiny blood vessels intertwine with urine-collecting tubes. Each kidney contains about 1 million nephrons.

At first, the tubules receive a combination of waste materials and chemicals the body can still use. The kidneys measure out chemicals like sodium, phosphorus, and potassium and release them back to the blood to return to the body. In this way, the kidneys regulate the body’s level of these substances. The right balance is necessary for life.

In addition to removing wastes, the kidneys release three important hormones:

• erythropoietin, or EPO, which stimulates the bone marrow to make red blood cells
• renin, which regulates blood pressure
• calcitriol, the active form of vitamin D, which helps maintain calcium for bones and for normal chemical balance in the body

Your Urinary System and How It Works

The organs, tubes, muscles, and nerves that work together to create, store, and carry urine are the urinary system. The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the urethra.

How does the urinary system work?

Front view of urinary tract.

Your body takes nutrients from food and uses them to maintain all bodily functions including energy and self-repair. After your body has taken what it needs from the food, waste products are left behind in the blood and in the bowel. The urinary system works with the lungs, skin, and intestines—all of which also excrete wastes—to keep the chemicals and water in your body balanced. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing. Certain types of medications can also affect the amount of urine eliminated.

The urinary system removes a type of waste called urea from your blood. Urea is produced when foods containing protein, such as meat, poultry, and certain vegetables, are broken down in the body. Urea is carried in the bloodstream to the kidneys.

The kidneys are bean-shaped organs about the size of your fists. They are near the middle of the back, just below the rib cage. The kidneys remove urea from the blood through tiny filtering units called nephrons. Each nephron consists of a ball formed of small blood capillaries, called a glomerulus, and a small tube called a renal tubule. Urea, together with water and other waste substances, forms the urine as it passes through the nephrons and down the renal tubules of the kidney.

From the kidneys, urine travels down two thin tubes called ureters to the bladder. The ureters are about 8 to 10 inches long. Muscles in the ureter walls constantly tighten and relax to force urine downward away from the kidneys. If urine is allowed to stand still, or back up, a kidney infection can develop. Small amounts of urine are emptied into the bladder from the ureters about every 10 to 15 seconds.

The bladder is a hollow muscular organ shaped like a balloon. It sits in your pelvis and is held in place by ligaments attached to other organs and the pelvic bones. The bladder stores urine until you are ready to go to the bathroom to empty it. It swells into a round shape when it is full and gets smaller when empty. If the urinary system is healthy, the bladder can hold up to 16 ounces (2 cups) of urine comfortably for 2 to 5 hours.

Circular muscles called sphincters help keep urine from leaking. The sphincter muscles close tightly like a rubber band around the opening of the bladder into the urethra, the tube that allows urine to pass outside the body.

Nerves in the bladder tell you when it is time to urinate, or empty your bladder. As the bladder first fills with urine, you may notice a feeling that you need to urinate. The sensation to urinate becomes stronger as the bladder continues to fill and reaches its limit. At that point, nerves from the bladder send a message to the brain that the bladder is full, and your urge to empty your bladder intensifies.

When you urinate, the brain signals the bladder muscles to tighten, squeezing urine out of the bladder. At the same time, the brain signals the sphincter muscles to relax. As these muscles relax, urine exits the bladder through the urethra. When all the signals occur in the correct order, normal urination occurs.

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What causes problems in the urinary system?

Problems in the urinary system can be caused by aging, illness, or injury. As you get older, changes in the kidneys’ structure cause them to lose some of their ability to remove wastes from the blood. Also, the muscles in your ureters, bladder, and urethra tend to lose some of their strength. You may have more urinary infections because the bladder muscles do not tighten enough to empty your bladder completely. A decrease in strength of muscles of the sphincters and the pelvis can also cause incontinence, the unwanted leakage of urine. Illness or injury can also prevent the kidneys from filtering the blood completely or block the passage of urine.

[Top]

How are problems in the urinary system detected?

Urinalysis is a test that studies the content of urine for abnormal substances such as protein or signs of infection. This test involves urinating into a special container and leaving the sample to be studied.

Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through the urethra. Your doctor may want to do a urodynamic test if you are having symptoms that suggest problems with the muscles or nerves of your lower urinary system and pelvis—ureters, bladder, urethra, and sphincter muscles.

Urodynamic tests measure the contraction of the bladder muscle as it fills and empties. The test is done by inserting a small tube called a catheter through your urethra into your bladder to fill it either with water or a gas. Another small tube is inserted into your rectum or vagina to measure the pressure put on your bladder when you strain or cough. Other bladder tests use x-ray dye instead of water so that x-ray pictures can be taken when the bladder fills and empties to detect any abnormalities in the shape and function of the bladder. These tests take about an hour.

The Kidneys and How They Work

What do the kidneys do?

The kidneys are bean-shaped organs, each about the size of a fist. They are located near the middle of the back, just below the rib cage, one on each side of the spine. The kidneys are sophisticated reprocessing machines. Every day, a person’s kidneys process about 200 quarts of blood to sift out about 2 quarts of waste products and extra water. The wastes and extra water become urine, which flows to the bladder through tubes called ureters. The bladder stores urine until releasing it through urination.

The kidneys remove wastes and water from the blood to form urine. Urine flows from the kidneys to the bladder through the ureters.

Wastes in the blood come from the normal breakdown of active tissues, such as muscles, and from food. The body uses food for energy and self-repairs. After the body has taken what it needs from food, wastes are sent to the blood. If the kidneys did not remove them, these wastes would build up in the blood and damage the body.

The actual removal of wastes occurs in tiny units inside the kidneys called nephrons. Each kidney has about a million nephrons. In the nephron, a glomerulus—which is a tiny blood vessel, or capillary—intertwines with a tiny urine-collecting tube called a tubule. The glomerulus acts as a filtering unit, or sieve, and keeps normal proteins and cells in the bloodstream, allowing extra fluid and wastes to pass through. A complicated chemical exchange takes place, as waste materials and water leave the blood and enter the urinary system.

In the nephron (left), tiny blood vessels intertwine with urine-collecting tubes. Each kidney contains about 1 million nephrons.

At first, the tubules receive a combination of waste materials and chemicals the body can still use. The kidneys measure out chemicals like sodium, phosphorus, and potassium and release them back to the blood to return to the body. In this way, the kidneys regulate the body’s level of these substances. The right balance is necessary for life.

In addition to removing wastes, the kidneys release three important hormones:

• erythropoietin, or EPO, which stimulates the bone marrow to make red blood cells
• renin, which regulates blood pressure
• calcitriol, the active form of vitamin D, which helps maintain calcium for bones and for normal chemical balance in the body

Analgesic Nephropathy (Painkillers and the Kidneys)

An analgesic is any medicine intended to relieve pain. Over-the-counter analgesics—that is, painkillers available without a prescription—include aspirin, acetaminophen, ibuprofen, naproxen sodium, and others. These drugs present no danger for most people when taken in the recommended dosage. But some conditions make taking even these common painkillers dangerous for the kidneys. Also, taking one of these drugs regularly over a long period of time may increase the risk for kidney problems. Most drugs that can cause kidney damage are excreted only through the kidneys. That is, they are not broken down by the liver, as alcohol is, or passed out of the body through the digestive tract.

Analgesic use has been associated with two different forms of kidney damage: acute renal failure and a type of chronic kidney disease called analgesic nephropathy.

Acute Kidney Failure

Some patient case reports have attributed incidents of sudden-onset acute kidney failure to the use of over-the-counter painkillers, including aspirin, ibuprofen, and naproxen sodium. Some of these patients experienced acute illnesses involving fluid loss or decreased fluid intake. Other patients in these reports had risk factors such as systemic lupus erythematosus, advanced age, chronic kidney disease, or recent heavy alcohol consumption. These cases involved a single dose in some instances and generally short-term analgesic use of not more than 10 days.

Acute kidney failure requires emergency dialysis to clean the blood. Kidney damage is frequently reversible, with normal kidney function returning after the emergency is over and the analgesic use is stopped.

Analgesic Nephropathy

A second form of kidney damage, called analgesic nephropathy, can result from taking painkillers every day for several years. Analgesic nephropathy is a chronic kidney disease that over years gradually leads to irreversible kidney failure and the permanent need for dialysis or a kidney transplant to restore kidney function. Researchers estimate that four out of 100,000 people will develop analgesic nephropathy. It is most common in women over 30.

The painkiller phenacetin has been taken off the market because of its association with analgesic nephropathy. Recent studies have suggested that longstanding daily use of analgesics such as acetaminophen or ibuprofen may also increase the risk of chronic kidney damage, but this evidence is not as clear.

In view of these findings, people with conditions that put them at risk for acute kidney failure should check with their health care provider before taking any analgesic medicine. People who take over-the-counter painkillers regularly should check with their primary care physician to make sure the drugs are not hurting their kidneys. The physician may be able to recommend a safer alternative and can order regular tests to monitor their kidney function.

Treatment

If you have been taking analgesics regularly to control chronic pain, you may be advised to find new ways to treat your pain, such as behavior modification or relaxation techniques. Depending on how much your kidney function has declined, you may be advised to change your diet, limit the fluids you drink, or take medications to avoid anemia and bone problems caused by kidney disease. Your doctor will monitor your kidney function with regular urine and blood tests.