HNSC 3162 Biological Concepts in Public Health (Cai)

About Chronic Diseases (CDC)

Chronic diseases are defined broadly as conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both. Chronic diseases such as heart disease, cancer, and diabetes are the leading causes of death and disability in the United States. They are also leading drivers of the nation’s $4.1 trillion in annual health care costs.

Three major Chronic Diseases are: heart disease, cancer, and diabetes.

Learning Objectives:

By the end of this section, you will be able to:

• recognize the key anatomical structures of the respiratory system.
• recognize the respiratory structural changes from asthma.
• summarize the signs and symptoms, triggers, diagnosis and treatment options for asthma.
• summarize why certain racial and ethnic groups have higher rates of asthma.

Content

Respiratory System

The major organs of the respiratory system function primarily to provide oxygen to body tissues for cellular respiration, remove the waste product carbon dioxide, and help to maintain acid-base balance. Portions of the respiratory system are also used for non-vital functions such as sensing odors, speech production, and for straining such as during childbirth or coughing.

The conducting zone consists of all of the structures that provide passageways for air to travel into and out of the lungs: the nasal cavity, pharynx, larynx, trachea, bronchi, and most bronchioles. The nasal passages contain the conchae and meatuses that expand the surface area of the cavity which helps to warm and humidify incoming air while removing debris and pathogens. The respiratory zone includes the structures of the lung that are directly involved in gas exchange: the terminal bronchioles and alveoli.

Anatomy:

Conducting Zone:

the main function of the conducting zone structures is to provide a passageway for air to move into and out of each lung. In addition, the mucous membrane traps debris and pathogens.

• The Nose: the major entrance and exit for the respiratory system.
• The pharynx: a tube formed by skeletal muscle that is continuous with the nasal cavities.
•  The Larynx:
  • a cartilaginous structure that connects the pharynx to the trachea and helps regulate the volume of air that enters and leaves the lungs.
  • the vocal cords are located here for producing voices.
  • The trachea (windpipe):  extends from the larynx toward the lungs.
  • Bronchial tree: the trachea branches into the right and left primary bronchi. They further branch into smaller tubes (bronchioles) to form the bronchial tree, which lead to the structures of gas exchange.

Respiratory Zone:

• Alveoli: is a cluster of many individual alveoli that are responsible for gas exchange.

Asthma Overview

Asthma is a common condition that affects the lungs in both adults and children. Approximately 8.2 percent of adults (18.7 million) and 9.4 percent of children (7 million) in the United States suffer from asthma. In addition, asthma is the most frequent cause of hospitalization in children.

Asthma is a chronic disease characterized by inflammation and edema of the airway and bronchospasms (that is, constriction of the bronchioles), which can inhibit air from entering the lungs. In addition, excessive mucus secretion can occur which further contributes to airway occlusion.

Bronchospasms occur periodically and lead to an “asthma attack.” An attack may be triggered by environmental factors such as dust, pollen, pet hair, or dander, changes in the weather, mold, tobacco smoke, and respiratory infections, or by exercise and stress.

An asthma attack includes thickened mucosa, increased mucus-producing goblet cells, and eosinophil infiltrates. (Figure 1)

Symptoms

Symptoms of an asthma attack involve coughing, shortness of breath, wheezing, and tightness of the chest. Symptoms of a severe asthma attack that requires immediate medical attention would include difficulty breathing that results in blue (cyanotic) lips or face, confusion, drowsiness, a rapid pulse, sweating, and severe anxiety. The severity of the condition, frequency of attacks, and identified triggers influence the type of medication that an individual may require. Longer-term treatments are used for those with more severe asthma. Short-term, fast-acting drugs that are used to treat an asthma attack are typically administered via an inhaler. For young children or individuals who have difficulty using an inhaler, asthma medications can be administered via a nebulizer.

Cause

In many cases, the underlying cause of the condition is unknown. However, recent research has demonstrated that certain viruses, such as human rhinovirus C (HRVC), and the bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae that are contracted in infancy or early childhood, may contribute to the development of many cases of asthma.

Trigger of Asthma

Asthma symptoms can appear when you are exposed to a trigger. A trigger is something you are sensitive to that makes your airways become inflamed. This causes swelling, mucus production, and narrowing in your airways. Common asthma triggers are pollen, air pollution, animal allergens, scents/fragrances, certain gases, extreme weather changes, smoke, dust mites, stress, and exercise.

Diagnosis of Asthma

A doctor may use a few different ways to look for asthma. These include:

• Taking a detailed medical history
• A physical exam
• Lung function tests
• Chest or sinus X-ray
• Blood tests to look for certain markers
• Allergy tests

The doctor will look at the results from these tests. They will then decide what type of asthma you have. They will develop a treatment plan based on the type and severity of your symptoms.

Types of asthma medicines and treatments:

1. Quick-relief medicines – These medicines work quickly to relieve sudden symptoms. You take them as needed and at the first sign of symptoms.
2. Controller medicines – These medicines help control asthma by correcting the underlying changes in the airways, such as swelling and excess mucus. They can be one or a combination of medicines.
3. Combination of quick-relief and controller medicines – These medicines are used for both short-term relief and control.
4. Biologics – This type of treatment targets a cell or protein to prevent swelling inside the airways. They are for people with certain types of persistent asthma and are given by injection or infusion.

Although medicines help a lot, they may not be able to do the job alone. You have to avoid the things that cause or trigger your asthma symptoms as much as you can. Asthma triggers can be found outside or inside your home, school, or workplace.

Improving the indoor air quality in your home is an important part of asthma control. Your indoor air can be more polluted than outside air. The interactive Healthy Home by the Asthma and Allergy Foundation of America can show you ways to improve the indoor air quality of your home. A healthier home can reduce your exposure to allergens and irritants.

Why Do Certain Racial or Ethnic Groups Have Higher Rates of Asthma, Asthma Attacks, or Asthma Deaths?

Racial and ethnic differences in asthma frequency, illness, and death are caused by complex factors, including:

• Structural determinants such as systemic racism, segregation, and discriminatory policies
• Social determinants such as socioeconomic status, education, neighborhood and physical environment, employment, social support networks, and access to health care
• Biological determinants such as genes and ancestry
• Behavioral determinants such as tobacco use and adherence to medicines.
• Social determinants and structural inequities (systemic racism) largely drive disparities in asthma. Factors such as genetics and individual behaviors contribute less to asthma disparities.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• define cancer.
• differentiate between benign tumors and cancerous tumors.
• recognize characteristics of cancer that are different from normal cells.
• summarize types of genes that cause cancer.
• describe the consequences of cancer metastasis.
• summarize tissue changes that are not cancer.

Content

Definition of Cancer (NIH)

Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body. 

Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and multiply (through a process called cell division) to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place.

Sometimes this orderly process breaks down, and abnormal or damaged cells grow and multiply when they shouldn’t. These cells may form tumors, which are lumps of tissue. Tumors can be cancerous or not cancerous (benign). 

Cancerous tumors spread into, or invade, nearby tissues and can travel to distant places in the body to form new tumors (a process called metastasis). Cancerous tumors may also be called malignant tumors. Many cancers form solid tumors, but cancers of the blood, such as leukemias, generally do not.

Benign tumors do not spread into, or invade, nearby tissues. When removed, benign tumors usually don’t grow back, whereas cancerous tumors sometimes do. Benign tumors can sometimes be quite large, however. Some can cause serious symptoms or be life threatening, such as benign tumors in the brain.

Differences between Cancer Cells and Normal Cells

Cancer cells differ from normal cells in many ways. For instance, cancer cells:

• grow in the absence of signals telling them to grow. Normal cells only grow when they receive such signals. 
• ignore signals that normally tell cells to stop dividing or to die (a process known as programmed cell death, or apoptosis).
• invade into nearby areas and spread to other areas of the body. Normal cells stop growing when they encounter other cells, and most normal cells do not move around the body. 
• tell blood vessels to grow toward tumors.  These blood vessels supply tumors with oxygen and nutrients and remove waste products from tumors.
• hide from the immune system. The immune system normally eliminates damaged or abnormal cells. 
• trick the immune system into helping cancer cells stay alive and grow. For instance, some cancer cells convince immune cells to protect the tumor instead of attacking it.
• accumulate multiple changes in their chromosomes, such as duplications and deletions of chromosome parts. Some cancer cells have double the normal number of chromosomes.
• rely on different kinds of nutrients than normal cells. In addition, some cancer cells make energy from nutrients in a different way than most normal cells. This lets cancer cells grow more quickly. 

Many times, cancer cells rely so heavily on these abnormal behaviors that they can’t survive without them. Researchers have taken advantage of this fact, developing therapies that target the abnormal features of cancer cells. For example, some cancer therapies prevent blood vessels from growing toward tumors, essentially starving the tumor of needed nutrients.

How Does Cancer Develop?

Cancer is a genetic disease—that is, it is caused by changes to genes that control the way our cells function, especially how they grow and divide. (Figure 2.1)

Genetic changes that cause cancer can happen because:

• of errors that occur as cells divide. 
• of damage to DNA caused by harmful substances in the environment, such as the chemicals in tobacco smoke and ultraviolet rays from the sun. (Our Cancer Causes and Prevention section has more information.) 
• they were inherited from our parents. 

The body normally eliminates cells with damaged DNA before they turn cancerous. But the body’s ability to do so goes down as we age. This is part of the reason why there is a higher risk of cancer later in life.

Each person’s cancer has a unique combination of genetic changes. As the cancer continues to grow, additional changes will occur. Even within the same tumor, different cells may have different genetic changes.

Types of Genes that Cause Cancer

The genetic changes that contribute to cancer tend to affect three main types of genes—proto-oncogenes, tumor suppressor genes, and DNA repair genes. These changes are sometimes called “drivers” of cancer.

Proto-oncogenes are involved in normal cell growth and division. However, when these genes are altered in certain ways or are more active than normal, they may become cancer-causing genes (or oncogenes), allowing cells to grow and survive when they should not.

Tumor suppressor genes are also involved in controlling cell growth and division. Cells with certain alterations in tumor suppressor genes may divide in an uncontrolled manner.

DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these genes tend to develop additional mutations in other genes and changes in their chromosomes, such as duplications and deletions of chromosome parts. Together, these mutations may cause the cells to become cancerous.

As scientists have learned more about the molecular changes that lead to cancer, they have found that certain mutations commonly occur in many types of cancer. Now there are many cancer treatments available that target gene mutations found in cancer. A few of these treatments can be used by anyone with a cancer that has the targeted mutation, no matter where the cancer started growing.

When Cancer Spreads

A cancer that has spread from the place where it first formed to another place in the body is called metastatic cancer. The process by which cancer cells spread to other parts of the body is called metastasis. (Figure 2.2)

Metastatic cancer has the same name and the same type of cancer cells as the original, or primary, cancer. For example, breast cancer that forms a metastatic tumor in the lung is metastatic breast cancer, not lung cancer.

Under a microscope, metastatic cancer cells generally look the same as cells of the original cancer. Moreover, metastatic cancer cells and cells of the original cancer usually have some molecular features in common, such as the presence of specific chromosome changes.

In some cases, treatment may help prolong the lives of people with metastatic cancer. In other cases, the primary goal of treatment for metastatic cancer is to control the growth of the cancer or to relieve symptoms it is causing. Metastatic tumors can cause severe damage to how the body functions, and most people who die of cancer die of metastatic disease.  

Tissue Changes that Are Not Cancer

Not every change in the body’s tissues is cancer. Some tissue changes may develop into cancer if they are not treated, however. Here are some examples of tissue changes that are not cancer but, in some cases, are monitored because they could become cancer: (Figure 2.3)

• Hyperplasia occurs when cells within a tissue multiply faster than normal and extra cells build up. However, the cells and the way the tissue is organized still look normal under a microscope. Hyperplasia can be caused by several factors or conditions, including chronic irritation.
• Dysplasia is a more advanced condition than hyperplasia. In dysplasia, there is also a buildup of extra cells. But the cells look abnormal and there are changes in how the tissue is organized. In general, the more abnormal the cells and tissue look, the greater the chance that cancer will form. Some types of dysplasia may need to be monitored or treated, but others do not. An example of dysplasia is an abnormal mole (called a dysplastic nevus) that forms on the skin. A dysplastic nevus can turn into melanoma, although most do not.
• Carcinoma in situ is an even more advanced condition. Although it is sometimes called stage 0 cancer, it is not cancer because the abnormal cells do not invade nearby tissue the way that cancer cells do. But because some carcinomas in situ may become cancer, they are usually treated.

Risk factors for cancer :

It is usually not possible to know exactly why one person develops cancer and another doesn’t. But research has shown that certain risk factors may increase a person’s chances of developing cancer. (There are also factors that are linked to a lower risk of cancer. These are called protective factors.)

Cancer risk factors include exposure to chemicals or other substances, as well as certain behaviors. They also include things people cannot control, like age and family history. A family history of certain cancers can be a sign of a possible inherited cancer syndrome.

Most cancer risk (and protective) factors are initially identified in epidemiology studies. In these studies, scientists look at large groups of people and compare those who develop cancer with those who don’t. These studies may show that the people who develop cancer are more or less likely to behave in certain ways or to be exposed to certain substances than those who do not develop cancer.

Such studies, on their own, cannot prove that a behavior or substance causes cancer. For example, the finding could be a result of chance, or the true risk factor could be something other than the suspected risk factor. But findings of this type sometimes get attention in the media, and this can lead to wrong ideas about how cancer starts and spreads.

When many studies all point to a similar association between a potential risk factor and an increased risk of cancer, and when a possible mechanism exists that could explain how the risk factor could actually cause cancer, scientists can be more confident about the relationship between the two.

The list below includes the most studied known or suspected risk factors for cancer. Although some of these risk factors can be avoided, others—such as growing older—cannot. Limiting your exposure to avoidable risk factors may lower your risk of developing certain cancers. Click on each risk factor below to find out more:

• Age
• Alcohol
• Cancer-Causing Substances
• Chronic Inflammation
• Diet
• Hormones
• Immuno suppression
• Infectious Agents
• Obesity
• Radiation
• Sunlight
• Tobacco

Alcohol

Tobacco

Tobacco use is a leading cause of cancer and of death from cancer. People who use tobacco products or who are regularly around environmental tobacco smoke (also called secondhand smoke) have an increased risk of cancer because tobacco products and secondhand smoke have many chemicals that damage DNA.

Tobacco use causes many types of cancer, including cancer of the lung, larynx (voice box), mouth, esophagus, throat, bladder, kidney, liver, stomach, pancreas, colon and rectum, and cervix, as well as acute myeloid leukemia. People who use smokeless tobacco (snuff or chewing tobacco) have increased risks of cancers of the mouth, esophagus, and pancreas.

There is no safe level of tobacco use. People who use any type of tobacco product are strongly urged to quit. People who quit smoking, regardless of their age, have substantial gains in life expectancy compared with those who continue to smoke. Also, quitting smoking at the time of a cancer diagnosis reduces the risk of death.

Scientists believe that cigarette smoking causes about 30% of all cancer deaths in the United States.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• identify the symptoms, risk factors, prevention and treatment options for lung cancer.

Content

Lung cancer includes two main types: non-small cell lung cancer and small cell lung cancer. Smoking causes most lung cancers, but nonsmokers can also develop lung cancer. These categories refer to what cancer cells look like under a microscope. Non-small cell lung cancer is more common than small cell lung cancer.

Symptoms

Different people have different symptoms for lung cancer. Some people have symptoms related to the lungs. Some people whose lung cancer has spread to other parts of the body (metastasized) have symptoms specific to that part of the body. Some people just have general symptoms of not feeling well. Most people with lung cancer don’t have symptoms until the cancer is advanced. Lung cancer symptoms may include—

• Coughing that gets worse or doesn’t go away.
• Chest pain.
• Shortness of breath.
• Wheezing.
• Coughing up blood.
• Feeling very tired all the time.
• Weight loss with no known cause.

Other changes that can sometimes occur with lung cancer may include repeated bouts of pneumonia and swollen or enlarged lymph nodes (glands) inside the chest in the area between the lungs.

These signs and symptoms can happen with other illnesses, too. If you have some of these signs and symptoms, talk to your doctor, who can help find the cause.

Risk Factors

• Smoking

Cigarette smoking is the number one risk factor for lung cancer. In the United States, cigarette smoking is linked to about 80% to 90% of lung cancer deaths. Using other tobacco products such as cigars or pipes also increases the risk for lung cancer. Tobacco smoke is a toxic mix of more than 7,000 chemicals. Many are poisons. At least 70 are known to cause cancer in people or animals.

People who smoke cigarettes are 15 to 30 times more likely to get lung cancer or die from lung cancer than people who do not smoke. Even smoking a few cigarettes a day or smoking occasionally increases the risk of lung cancer. The more years a person smokes and the more cigarettes smoked each day, the more risk goes up.

People who quit smoking have a lower risk of lung cancer than if they had continued to smoke, but their risk is higher than the risk for people who never smoked. Quitting smoking at any age can lower the risk of lung cancer.

Cigarette smoking can cause cancer almost anywhere in the body. Cigarette smoking causes cancer of the mouth and throat, esophagus, stomach, colon, rectum, liver, pancreas, voicebox (larynx), lung, trachea, bronchus, kidney and renal pelvis, urinary bladder, and cervix, and causes acute myeloid leukemia.

• Second-hand smoking
• Radon
• Other substances found at some workplaces that increase risk include asbestos, arsenic, diesel exhaust, and some forms of silica and chromium. For many of these substances, the risk of getting lung cancer is even higher for those who smoke. Living in areas with higher levels of air pollution may increase the risk of getting lung cancer.
• Personal or Family History of Lung Cancer
• Radiation Therapy to the Chest
• Cancer survivors who had radiation therapy to the chest are at higher risk of lung cancer.
• Diet

Types of Treatment

Lung cancer is treated in several ways, depending on the type of lung cancer and how far it has spread. People with non-small cell lung cancer can be treated with surgery, chemotherapy, radiation therapy, targeted therapy, or a combination of these treatments. People with small cell lung cancer are usually treated with radiation therapy and chemotherapy.

• Surgery. An operation where doctors cut out cancer tissue.
• Chemotherapy. Using special medicines to shrink or kill the cancer. The drugs can be pills you take or medicines given in your veins, or sometimes both.
• Radiation therapy. Using high-energy rays (similar to X-rays) to kill the cancer.
• Targeted therapy. Using drugs to block the growth and spread of cancer cells. The drugs can be pills you take or medicines given in your veins. You will get tests to see if targeted therapy is right for your cancer type before this treatment is used.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• recognize key anatomical components of the breast.
• identify the symptoms, risk/protective factors, prevention and treatment options for breast cancer.
• summarize the types of screening exams for breast cancer.

Content

Breast cancer is the second most common cancer in women after skin cancer. Mammograms can detect breast cancer early, possibly before it has spread.

Anatomy

The breast is made up of lobes and ducts. Each breast has 15 to 20 sections called lobes, which have many smaller sections called lobules. Lobules end in dozens of tiny bulbs that can make milk. The lobes, lobules, and bulbs are linked by thin tubes called ducts.(Figure 4)

Each breast also has blood vessels and lymph vessels. The lymph vessels carry an almost colorless, watery fluid called lymph. Lymph vessels carry lymph between lymph nodes. Lymph nodes are small, bean-shaped structures that filter lymph and store white blood cells that help fight infection and disease. Groups of lymph nodes are found near the breast in the axilla (under the arm), above the collarbone, and in the chest.

Symptoms: (CDC)

Different people have different symptoms of breast cancer. Some people do not have any signs or symptoms at all.

Some warning signs of breast cancer are—

• New lump in the breast or underarm (armpit).
• Thickening or swelling of part of the breast.
• Irritation or dimpling of breast skin.
• Redness or flaky skin in the nipple area or the breast.
• Pulling in of the nipple or pain in the nipple area.
• Nipple discharge other than breast milk, including blood.
• Any change in the size or the shape of the breast.
• Pain in any area of the breast.

Keep in mind that these symptoms can happen with other conditions that are not cancer.

Risk Factors (NIH)

Besides female sex, advancing age is the biggest risk factor for breast cancer. Reproductive factors that increase exposure to endogenous estrogen, such as early menarche and late menopause, increase risk, as does the use of combination estrogen-progesterone hormones after menopause. Nulliparity and alcohol consumption also are associated with increased risk.

Women with a family history or personal history of invasive breast cancer, ductal carcinoma in situ or lobular carcinoma in situ, or a history of breast biopsies that show benign proliferative disease have an increased risk of breast cancer.

Increased breast density is associated with increased risk. It is often a heritable trait but is also seen more frequently in nulliparous women, women whose first pregnancy occurs late in life, and women who use postmenopausal hormones and alcohol.

Exposure to ionizing radiation, especially during puberty or young adulthood, and the inheritance of detrimental genetic mutations increase breast cancer risk.

The Breast Cancer Risk Assessment Tool (BCRAT)

The Breast Cancer Risk Assessment Tool (BCRAT), also known as The Gail Model, allows health professionals to estimate a woman's risk of developing invasive breast cancer over the next five years and up to age 90 (lifetime risk).

The tool uses a woman's personal medical and reproductive history and the history of breast cancer among her first-degree relatives (mother, sisters, daughters) to estimate absolute breast cancer risk-her chance or probability of developing invasive breast cancer in a defined age interval.

This calculator takes about five minutes to complete.

Go to Calculate Patient Risk calculator

About the Calculator

The tool has been validated for White women, Black/African American women, Hispanic women, and for Asian and Pacific Islander women in the United States.

The tool may underestimate risk in Black women with previous biopsies and Hispanic women born outside the United States. Because data on American Indian/Alaska Native women are limited, their risk estimates are partly based on data for White women and may be inaccurate. Further studies are needed to refine and validate these models.

Calculator Limitations

This tool cannot accurately estimate breast cancer risk for:

• Women carrying a breast-cancer-producing mutation in BRCA1 or BRCA2
• Women with a previous history of invasive or in situ breast cancer (lobular carcinoma in situ or ductal carcinoma in situ)
• Women in certain other subgroups (see Other Risk Assessment Tools section)

Although a woman's risk may be accurately estimated, these predictions do not allow one to say precisely which woman will develop breast cancer. In fact, some women who do not develop breast cancer have higher risk estimates than some women who do develop breast cancer.

Reduce the Risk of Breast Cancer (CDC)

• Many factors over the course of a lifetime can influence your breast cancer risk. You can’t change some factors, such as getting older or your family history, but you can help lower your risk of breast cancer by taking care of your health in the following ways—
• Keep a healthy weight.
• Be physically active.
• Choose not to drink alcohol, or drink alcohol in moderation.
• If you are taking, or have been told to take, hormone replacement therapy or oral contraceptives (birth control pills), ask your doctor about the risks and find out if it is right for you.
• Breastfeed your children, if possible.
• If you have a family history of breast cancer or inherited changes in your BRCA1 and BRCA2 genes, talk to your doctor about other ways to lower your risk.
• Staying healthy throughout your life will lower your risk of developing cancer, and improve your chances of surviving cancer if it occurs.

Factors with adequate evidence of decreased risk of breast cancer (according to National Cancer Institute of NIH)

• Early Pregnancy
• Breast-feeding
• Exercise

Screening

• Tests are used to screen for different types of cancer when a person does not have symptoms.
• Mammography is the most common screening test for breast cancer.
• Magnetic resonance imaging (MRI) may be used to screen women who have a high risk of breast cancer.
• Whether a woman should be screened for breast cancer and the screening test to use depends on certain factors.
• Other screening tests have been or are being studied in clinical trials.
  • Breast Exam
  • Thermography
  • Tissue sampling

Treatment

Breast cancer is treated in several ways. It depends on the kind of breast cancer and how far it has spread. People with breast cancer often get more than one kind of treatment.

• Surgery. An operation where doctors cut out the cancer.
• Chemotherapy. Using special medicines to shrink or kill the cancer cells. The drugs can be pills you take or medicines given in your veins, or sometimes both.
• Hormonal therapy. Blocks cancer cells from getting the hormones they need to grow.
• Biological therapy. Works with your body’s immune system to help it fight cancer cells or to control side effects from other cancer treatments.
• Radiation therapy. Using high-energy rays (similar to X-rays) to kill the cancer cells.

Doctors from different specialties often work together to treat breast cancer. Surgeons are doctors who perform operations. Medical oncologists are doctors who treat cancer with medicine. Radiation oncologists are doctors who treat cancer with radiation.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• identify the symptoms, risk/protective factors, prevention and treatment options for colorectal cancer.
• recognize key anatomical components of the digestive system.

Content

Colorectal cancer is a disease in which malignant (cancer) cells form in the tissues of the colon or the rectum. Colorectal cancer is the third leading cause of death from cancer in the United States.

Anatomy

Symptoms: (CDC)n

Colorectal polyps (abnormal growths in the colon or rectum that can turn into cancer if not removed) and colorectal cancer don’t always cause symptoms, especially at first. Someone could have polyps or colorectal cancer and not know it. That is why getting screened regularly for colorectal cancer is so important.

If you have symptoms, they may include—

• A change in bowel habits.
• Blood in or on your stool (bowel movement).
• Diarrhea, constipation, or feeling that the bowel does not empty all the way.
• Abdominal pain, aches, or cramps that don’t go away.
• Weight loss and you don’t know why.

Factors With Adequate Evidence of Increased Risk of Colorectal Cancer

• Excessive alcohol use
• Cigarette smoking
• Obesity
• Family/personal history of colorectal cancer and other hereditary conditions

Factors With Adequate Evidence for a Decreased Risk of Colorectal Cancer

• Physical activity

Screening:

Most people should begin screening for colorectal cancer soon after turning 45, then continue getting screened at regular intervals. However, you may need to be tested earlier than 45, or more often than other people, if you have—

• Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis.
• A personal or family history of colorectal cancer or colorectal polyps.
• A genetic syndrome such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (Lynch syndrome).

Treatment

Seven types of standard treatment are used:

• Surgery
• Radiofrequency ablation
• Cryosurgery
• Chemotherapy
• Radiation therapy
• Targeted therapy
• Immunotherapy

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• recognize key anatomical components of the heart.
• differentiate between pulmonary circulation and systemic circulation.
• trace the pathway of oxygenated and deoxygenated blood through the chambers of the heart.
• describe the function of this coronary circulation.
• briefly describe different types of cardiovascular diseases.
• summarize the risk factors for cardiovascular diseases.

Content

Section 1: Anatomy and function of the heart

The vital importance of the heart is obvious. If one assumes an average rate of contraction of 75 contractions per minute, a human heart would contract approximately 108,000 times in one day, more than 39 million times in one year and nearly 3 billion times during a 75-year lifespan! Each of the major pumping chambers of the heart ejects approximately 70 mL blood per contraction in a resting adult. This would be equal to 5.25 litres of fluid per minute and approximately 14,000 litres per day. Over one year, that would equal 10,000,000 litres (2.6 million gallons) of blood sent through roughly 97,000 kilometres (60,000 miles) of vessels. In order to understand how that happens, it is necessary to understand the anatomy and physiology of the heart.

Chambers and Circulation Through the Heart

The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle. Each of the upper chambers, the right atrium (plural = atria) and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body.

There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. The systemic circuit transports oxygenated blood to virtually all the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation.

The right ventricle pumps deoxygenated blood into the pulmonary trunk, which leads toward the lungs and bifurcates into the left and right pulmonary arteries. These vessels in turn branch many times before reaching the pulmonary capillaries, where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins—the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood.

The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava, which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions (Figure 6.1.3).

Heart Valves and Function

There are four valves in the heart. The valves ensure unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the right atrioventricular valve, or tricuspid valve.

Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve, or the pulmonary valve.

Located at the opening between the left atrium and left ventricle is the mitral valve, also called the bicuspid valve or the left atrioventricular valve.

At the base of the aorta is the aortic semilunar valve, or the aortic valve, which prevents backflow from the aorta.

Coronary Circulation

You will recall that the heart is a remarkable pump composed largely of cardiac muscle cells that are incredibly active throughout life. Like all other cells, a cardiomyocyte requires a reliable supply of oxygen and nutrients, and a way to remove wastes, so it needs a dedicated, complex, and extensive coronary circulation. And because of the critical and nearly ceaseless activity of the heart throughout life, this need for a blood supply is even greater than for a typical cell. 

Coronary arteries

Supply blood to the myocardium and other components of the heart. The first portion of the aorta after it arises from the left ventricle gives rise to the coronary arteries.

 Section 2: Cardiovascular Diseases

What are cardiovascular diseases?

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. They include:

• coronary heart disease – a disease of the blood vessels supplying the heart muscle;
• cerebrovascular disease – a disease of the blood vessels supplying the brain;
• peripheral arterial disease – a disease of blood vessels supplying the arms and legs;
• rheumatic heart disease – damage to the heart muscle and heart valves from rheumatic fever, caused by streptococcal bacteria;
• congenital heart disease – birth defects that affect the normal development and functioning of the heart caused by malformations of the heart structure from birth; and
• deep vein thrombosis and pulmonary embolism – blood clots in the leg veins, which can dislodge and move to the heart and lungs.

Heart attacks and strokes are usually acute events and are mainly caused by a blockage that prevents blood from flowing to the heart or brain. The most common reason for this is a build-up of fatty deposits on the inner walls of the blood vessels that supply the heart or brain. Strokes can be caused by bleeding from a blood vessel in the brain or from blood clots.

1. Function of the heart
2. What is atherosclerosis?
3. What is another name for heart disease?
4. What is ischemia?
5. What is angina?
6. What is thrombosis?
7. What is infarction?
8. What is a heart attack?
9. What is cardiac arrest?

Diseases of the Heart: Coronary Artery Disease

Coronary artery disease is the leading cause of death worldwide. It occurs when the build-up of plaque—a fatty material including cholesterol, connective tissue, white blood cells, and some smooth muscle cells—within the walls of the arteries obstructs the flow of blood and decreases the flexibility or compliance of the vessels. This condition is called atherosclerosis, a hardening of the arteries that involves the accumulation of plaque. As the coronary blood vessels become occluded, the flow of blood to the tissues will be restricted, a condition called ischaemia that causes the cells to receive insufficient amounts of oxygen, called hypoxia. Figure 6.1.15 shows the blockage of coronary arteries highlighted by the injection of dye. Some individuals with coronary artery disease report pain radiating from the chest called angina pectoris, but others remain asymptomatic. If untreated, coronary artery disease can lead to MI or a heart attack.

Risk Factors

Leading risk factors for heart disease and stroke are high blood pressure, high low-density lipoprotein (LDL) cholesterol, diabetes, smoking and secondhand smoke exposure, obesity, unhealthy diet, and physical inactivity.

High blood pressure

High blood pressure is a leading cause of heart disease and stroke because it damages the lining of the arteries, making them more susceptible to the buildup of plaque, which narrows the arteries leading to the heart and brain. About 116 million US adults (nearly 1 in 2) have high blood pressure, defined as 130/80 mm Hg or higher. Only about 1 in 4 of these people have their high blood pressure under control. About 7 in 10 people who have a first heart attack and 8 in 10 people who have a first stroke have high blood pressure.

Eating too much sodium can lead to high blood pressure. Americans aged 2 years or older consume an average of about 3,400 mg of sodium each day, well over the 2,300 mg recommended by the Dietary Guidelines for Americans. More than 70% of the sodium Americans consume is added outside the home (before purchase), not added as salt at the table or during home cooking.

High LDL cholesterol

High LDL cholesterol can double a person’s risk of heart disease. That’s because excess cholesterol can build up in the walls of arteries and limit blood flow to a person’s heart, brain, kidneys, other organs, and legs. Although nearly 86 million US adults could benefit from taking medicine to manage their high LDL cholesterol, only about half (55%) are doing so.

Diabetes

Adults with diabetes are twice as likely to have heart disease or a stroke as people who do not have diabetes. Over time, high blood sugar from diabetes can damage blood vessels in the heart and block blood vessels leading to the brain, causing a stroke. More than 2 in 3 people with diabetes have high blood pressure. Diabetes also raises triglycerides and LDL cholesterol.

Smoking

Smoking is a major cause of heart disease and stroke and causes 1 in every 4 deaths from these conditions. Smoking can damage the body several ways by:

• Raising triglycerides (a type of fat in the blood) and lowering high-density lipoprotein (HDL) cholesterol, also called “good” cholesterol.
• Making blood sticky and more likely to clot, which can block blood flow to the heart and brain.
• Damaging cells that line the blood vessels.
• Increasing the buildup of plaque (fat, cholesterol, calcium, and other substances) in blood vessels.
• Causing thickening and narrowing of blood vessels.

About 34 million US adults smoke cigarettes, and every day, about 1,600 young people under age 18 try their first cigarette.

Overweight or Obesity

Compared to those at a normal weight, people with overweight or obesity are at increased risk of heart disease and stroke and their risk factors, including high blood pressure, high LDL cholesterol, low HDL cholesterol, high triglycerides, and type 2 diabetes. In the United States, nearly 74% of adults have overweight or obesity.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• distinguish between systolic pressure and diastolic pressure.
• identify and discuss five variables affecting arterial blood flow and blood pressure.
• recognize the mechanisms that regulate blood pressure.
• describe how the ADH, RAAS and ANP regulate the blood pressure.
• summarize the classification of hypertension.
• identify the risk factors of hypertension.
• summarize the management and prevention of hypertension.
• identify management strategies and lifestyle changes that control hypertension.
• recognize the medical treatment options for hypertension

Content

Section 1: Blood flow, blood pressure and the resistance

Blood flow (hemodynamics) 

refers to the movement of blood through a vessel, tissue, or organ, and is usually expressed in terms of volume of blood per unit of time. It is initiated by the contraction of the ventricles of the heart. Ventricular contraction ejects blood into the major arteries, resulting in flow from regions of higher pressure to regions of lower pressure, as blood encounters smaller arteries and arterioles, then capillaries, then the venules and veins of the venous system. This section discusses a number of critical variables that contribute to blood flow throughout the body. It also discusses the factors that impede or slow blood flow, a phenomenon known as resistance.

Hydrostatic pressure is the force exerted by a fluid due to gravitational pull, usually against the wall of the container in which it is located. One form of hydrostatic pressure is blood pressure, the force exerted by blood upon the walls of the blood vessels or the chambers of the heart. Blood pressure may be measured in capillaries and veins, as well as the vessels of the pulmonary circulation; however, the term blood pressure without any specific descriptors typically refers to systemic arterial blood pressure—that is, the pressure of blood flowing in the arteries of the systemic circulation. In clinical practice, this pressure is measured in mm Hg and is usually obtained using the brachial artery of the arm.

Components of Arterial Blood Pressure

Arterial blood pressure in the larger vessels consists of several distinct components (Figure 6.7.1): systolic and diastolic pressures, pulse pressure, and mean arterial pressure.

Systolic and Diastolic Pressure

When systemic arterial blood pressure is measured, it is recorded as a ratio of two numbers (e.g., 120/80 is a normal adult blood pressure), expressed as systolic pressure over diastolic pressure. The systolic pressure is the higher value (typically around 120 mm Hg) and reflects the arterial pressure resulting from the ejection of blood during ventricular contraction, or systole. The diastolic pressure is the lower value (usually about 80 mm Hg) and represents the arterial pressure of blood during ventricular relaxation, or diastole.

Pulse Pressure

As shown in Figure 6.7.1, the difference between the systolic pressure and the diastolic pressure is the pulse pressure. For example, an individual with a systolic pressure of 120 mm Hg and a diastolic pressure of 80 mm Hg would have a pulse pressure of 40 mmHg.

Mean Arterial Pressure

Mean arterial pressure (MAP) represents the “average” pressure of blood in the arteries, that is, the average force driving blood into vessels that serve the tissues. Mean is a statistical concept and is calculated by taking the sum of the values divided by the number of values.

Variables Affecting Blood Flow and Blood Pressure

Five variables influence blood flow and blood pressure:

• Cardiac output
• Compliance
• Volume of the blood
• Viscosity of the blood
• Blood vessel length and diameter

Blood moves from higher pressure to lower pressure. It is pumped from the heart into the arteries at high pressure. If you increase pressure in the arteries (afterload), and cardiac function does not compensate, blood flow will actually decrease. In the venous system, the opposite relationship is true. Increased pressure in the veins does not decrease flow as it does in arteries, but actually increases flow. Since pressure in the veins is normally relatively low, for blood to flow back into the heart, the pressure in the atria during atrial diastole must be even lower. It normally approaches zero, except when the atria contract. (see Figure 6.7.1).

Cardiac Output

Cardiac output is the measurement of blood flow from the heart through the ventricles and is usually measured in litres per minute. Any factor that causes cardiac output to increase, by elevating heart rate or stroke volume or both, will elevate blood pressure and promote blood flow.

Compliance

Compliance is the ability of any compartment to expand to accommodate increased content. A metal pipe, for example, is not compliant, whereas a balloon is. The greater the compliance of an artery, the more effectively it is able to expand to accommodate surges in blood flow without increased resistance or blood pressure. Veins are more compliant than arteries and can expand to hold more blood. When vascular disease causes stiffening of arteries, compliance is reduced and resistance to blood flow is increased. The result is more turbulence, higher pressure within the vessel, and reduced blood flow. This increases the work of the heart.

Blood Volume

The relationship between blood volume, blood pressure, and blood flow is intuitively obvious. Water may merely trickle along a creek bed in a dry season but rush quickly and under great pressure after a heavy rain. Similarly, as blood volume decreases, pressure and flow decrease. As blood volume increases, pressure and flow increase.

Blood Viscosity

Viscosity is the thickness of fluids that affects their ability to flow. Clean water, for example, is less viscous than mud. The viscosity of blood is directly proportional to resistance and inversely proportional to flow; therefore, any condition that causes viscosity to increase will also increase resistance and decrease flow.

Vessel Length and Diameter

The length of a vessel is directly proportional to its resistance: the longer the vessel, the greater the resistance and the lower the flow. As with blood volume, this makes intuitive sense, since the increased surface area of the vessel will impede the flow of blood. Likewise, if the vessel is shortened, the resistance will decrease and flow will increase.

The length of our blood vessels increases throughout childhood as we grow, of course, but is unchanging in adults under normal physiological circumstances. Further, the distribution of vessels is not the same in all tissues. Adipose tissue does not have an extensive vascular supply. One pound of adipose tissue contains approximately 200 miles of vessels, whereas skeletal muscle contains more than twice that.

In contrast to length, the diameter of blood vessels changes throughout the body, according to the type of vessel. The diameter of any given vessel may also change frequently throughout the day in response to neural and chemical signals that trigger vasodilation and vasoconstriction. The vascular tone of the vessel is the contractile state of the smooth muscle and the primary determinant of diameter, and thus of resistance and flow. The effect of vessel diameter on resistance is inverse: Given the same volume of blood, an increased diameter means there is less blood contacting the vessel wall, thus lower friction and lower resistance, subsequently increasing flow. A decreased diameter means more of the blood contacts the vessel wall, and resistance increases, subsequently decreasing flow.

The influence of lumen diameter on resistance is dramatic: A slight increase or decrease in diameter causes a huge decrease or increase in resistance.

Section 2: Regulation of Blood Pressure

In order to maintain homeostasis in the cardiovascular system and provide adequate blood to the tissues, blood flow must be redirected continually to the tissues as they become more active. In a very real sense, the cardiovascular system engages in resource allocation, because there is not enough blood flow to distribute blood equally to all tissues simultaneously. For example, when an individual is exercising, more blood will be directed to skeletal muscles, the heart, and the lungs. Following a meal, more blood is directed to the digestive system. Only the brain receives a more or less constant supply of blood whether you are active, resting, thinking, or engaged in any other activity.

Three homeostatic mechanisms ensure adequate blood flow, blood pressure, distribution, and ultimately perfusion: neural, endocrine, and autoregulatory mechanisms. They are summarized in Figure 6.9.1.

We will focus on endocrine control involving the kidneys as the kidneys play an important role in long-term level of arterial blood pressure regulation.

Antidiuretic Hormone (ADH)

Antidiuretic hormone (ADH), also known as vasopressin, is secreted by the cells in the hypothalamus. The primary trigger prompting the hypothalamus to release ADH is increasing osmolarity of tissue fluid, usually in response to significant loss of blood volume. ADH signals its target cells in the kidneys to reabsorb more water, thus preventing the loss of additional fluid in the urine. This will increase overall fluid levels and help restore blood volume and pressure. In addition, ADH constricts peripheral vessels.

Renin-Angiotensin-Aldosterone System (RAAS)

The renin-angiotensin-aldosterone mechanism has a major effect upon the cardiovascular system (Figure 6.9.3). Renin is an enzyme, although because of its importance in the renin-angiotensin-aldosterone pathway, some sources identify it as a hormone. Specialized cells in the kidneys found in the juxtaglomerular apparatus respond to decreased blood flow by secreting renin into the blood. Renin converts the plasma protein angiotensinogen, which is produced by the liver, into its active form—angiotensin I. Angiotensin I circulates in the blood and is then converted into angiotensin II in the lungs. This reaction is catalyzed by the enzyme angiotensin-converting enzyme (ACE).

Angiotensin II is a powerful vasoconstrictor, greatly increasing blood pressure. It also stimulates the release of ADH and aldosterone, a hormone produced by the adrenal cortex. Aldosterone increases the reabsorption of sodium into the blood by the kidneys. Since water follows sodium, this increases the reabsorption of water. This in turn increases blood volume, raising blood pressure. Angiotensin II also stimulates the thirst center in the hypothalamus, so an individual will likely consume more fluids, again increasing blood volume and pressure.

Atrial Natriuretic Peptide (ANP)

Secreted by cells in the atria of the heart, atrial natriuretic hormone (ANH) or also known as atrial natriuretic peptide, is secreted when blood volume is high enough to cause extreme stretching of the cardiac cells. Natriuretic hormones are antagonists to angiotensin II. They promote loss of sodium and water from the kidneys, and suppress renin, aldosterone and ADH production and release. All of these actions promote loss of fluid from the body, so blood volume and blood pressure drop.

Section 3: Hypertension (high blood pressure)

High blood pressure increases the risk for heart disease and stroke, two leading causes of death for Americans. High blood pressure is also very common. Tens of millions of adults in the United States have high blood pressure, and many do not have it under control. 

Symptoms

High blood pressure usually has no symptoms, so the only way to know if you have it is to get your blood pressure measured. 

Blood Pressure Levels (National Heart, lung and blood institute at NIH)

Your blood pressure changes throughout the day based on your activities. For most adults, a normal blood pressure is less than 120 over 80 millimeters of mercury (mm Hg), which is written as your systolic pressure reading over your diastolic pressure reading — 120/80 mm Hg. Your blood pressure is considered high when you have consistent systolic readings of 130 mm Hg or higher or diastolic readings of 80 mm Hg or higher.

Risk Factors

• Elevated Blood Pressure

  • Elevated blood pressure is blood pressure that is slightly higher than normal. High blood pressure usually develops over time. Having blood pressure that is slightly higher than normal increases your risk for developing chronic, or long-lasting, high blood pressure in the future.

• Diabetes

  • About 6 out of 10 of people who have diabetes also have high blood pressure.1 Diabetes causes sugars to build up in the blood and also increases the risk for heart disease.

• Unhealthy Diet

  • A diet that is too high in sodium and too low in potassium puts you at risk for high blood pressure.
  • Eating too much sodium—an element in table salt—increases blood pressure. Most of the sodium we eat comes from processed and restaurant foods.

• Physical Inactivity

  • Getting regular physical activity helps your heart and blood vessels stay strong and healthy, which may help lower your blood pressure.

• Obesity

  • Having obesity is having excess body fat. Having obesity or overweight also means your heart must work harder to pump blood and oxygen around your body. Over time, this can add stress to your heart and blood vessels.

• Too much alcohol

• Tobacco use

Prevention and Management of Hypertension

Healthy lifestyle changes

If you have high blood pressure, your provider may recommend that you adopt a heart-healthy lifestyle to help lower and control high blood pressure.

• Choose heart-healthy foods such as those in the DASH eating plan. NHLBI-funded research has shown that DASH combined with a low-salt eating plan can be as effective as medicines in lowering high blood pressure. Living With the DASH Eating Plan and Tips to Reduce Salt and Sodium offer more information.
• Avoid or limit alcohol. 
• Get regular physical activity. Many health benefits result from getting the recommended amount of physical activity each week. Studies have shown that physical activity can help lower and control high blood pressure levels. Even modest amounts of physical activity may help. Before starting any exercise program, ask your healthcare provider what level of activity is right for you
• Aim for a healthy weight. If you are an adult who is living with overweight or obesity, losing 5% to 10% of your initial weight over 6 months can improve your health. Even losing just 3% to 5% of your weight can improve blood pressure.
• Quit smoking
• Manage stress. Learning how to manage stress and cope with problems can improve your mental and physical health. Learning relaxation techniques, talking to a counselor, and finding a support group can all help.
• Get enough good-quality sleep. The recommended amount for adults is 7 to 9 hours of sleep per day. Develop healthy sleep habits by going to sleep and getting up at regular times, following a calming bedtime routine, and keeping your bedroom cool and dark.

Changing habits can be hard. To help make lifelong heart-healthy changes, try making one change at a time. Add another change when you feel comfortable with the previous one. You’re more likely to manage your blood pressure when you practice several of these healthy lifestyle habits together and can keep them up over time.

Medicines

When healthy lifestyle changes alone do not control or lower high blood pressure, your healthcare provider may prescribe blood pressure medicines. These medicines act in different ways to lower blood pressure. When prescribing medicines, your provider also considers their effect on other conditions you have, such as heart disease or kidney disease.

Keep up your healthy lifestyle changes while taking these medicines. The combination of medicines and heart-healthy lifestyle changes can help control and lower your high blood pressure and prevent heart disease.

• There are several very common possible high blood pressure medicines your provider may prescribe. Angiotensin-converting enzyme (ACE) inhibitors keep your blood vessels from narrowing as much.
• Angiotensin II receptor blockers (ARBs) keep blood vessels from narrowing.
• Calcium channel blockers prevent calcium from entering the muscle cells of your heart and blood vessels. This allows blood vessels to relax.
• Diuretics remove extra water and sodium (salt) from your body, reducing the amount of fluid in your blood. The main diuretic for high blood pressure treatment is thiazide. Diuretics are often used with other high blood pressure medicines, sometimes in one combined pill.
• Beta blockers help your heart beat slower and with less force. As a result, your heart pumps less blood through your blood vessels. Beta blockers are typically used only as a backup option or if you have other conditions.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• summarize the cause and health consequences of obesity.
• identify the major organs and tissues of the endocrine system and their location in the body.
• summarize the hormones produced by the adipose tissue and their functions.
• summarize how genetic factors influence obesity.

Section 1: Cause & Health Consequences of Obesity

What is obesity?

Weight that is higher than what is considered healthy for a given height is described as overweight or obesity. Body Mass Index (BMI) is a screening tool for overweight and obesity.

Cause of Obesity

Obesity is a complex disease that occurs when an individual’s weight is higher than what is considered healthy for his or her height. Obesity affects children as well as adults. Many factors can contribute to excess weight gain including eating patterns, physical activity levels, and sleep routines. Social determinants of health, genetics, and taking certain medications also play a role.

Food, Activity, and Sleep

Eating and physical activity patterns, insufficient sleep and several other factors influence excess weight gain.

Social Determinants of Health (SDOH)

The conditions in which we live, learn, work, and play are called social determinants of health (SDOH). It can be difficult to make healthy food choices and get enough physical activity if these conditions do not support health. Differences in SDOH affect chronic disease outcomes and risks, including obesity, among racial, ethnic, and socioeconomic groups as well as in different geographies and among people with different physical abilities.

Places such as childcare centers, schools, or communities affect eating patterns and activity through the foods and drinks they offer and the physical activity opportunities they provide. Other community factors that influence obesity include the affordability of healthy food options, peer and social supports, marketing and promotion, and policies that determine community design.

Genetics

Genetic changes in human populations occur too slowly to be responsible for the obesity epidemic. Yet variants in several genes may contribute to obesity by increasing hunger and food intake. Rarely, a specific variant of a single gene (monogenic obesity) causes a clear pattern of inherited obesity within a family.^[1], [2]

Illnesses and Medications

Some illnesses, such as Cushing’s disease, may lead to obesity or weight gain. Drugs such as steroids and some antidepressants may also cause weight gain. Research continues on the role of other factors such as chemical exposures and the role of the microbiome.

Health Consequences of Obesity

People who have obesity, compared to those with a healthy weight, are at increased risk for many serious diseases and health conditions. In addition, obesity and its associated health problems have a significant economic impact on the US health care system. Obesity also affects military readiness.

Obesity in children and adults increases the risk for the following health conditions:

• High blood pressure and high cholesterol which are risk factors for heart disease.
• Type 2 diabetes.
• Breathing problems, such as asthma and sleep apnea.
• Joint problems such as osteoarthritis and musculoskeletal discomfort.
• Gallstones and gallbladder disease.

Childhood obesity is also associated with:

• Psychological problems such as anxiety and depression.
• Low self-esteem and lower self-reported quality of life.
• Social problems such as bullying and stigma.
• Obesity as adults.

Adults with obesity have higher risks for stroke, many types of cancer, premature death, and mental illness such as clinical depression and anxiety.

Section 2: Endocrine System and Hormones that Signal Metabolism

An Overview of the Endocrine System

Communication is a process in which a sender transmits signals to one or more receivers to control and coordinate actions. In the human body, two major organ systems participate in relatively “long distance” communication: the nervous system and the endocrine system. Together, these two systems are primarily responsible for maintaining homeostasis in the body.

The nervous system uses two types of intercellular communication—electrical and chemical signaling—either by the direct action of an electrical potential, or in the latter case, through the action of chemical neurotransmitters such as serotonin or noradrenaline. Neurotransmitters act locally and rapidly.

In contrast, the endocrine system uses just one method of communication: chemical signaling. These signals are sent by the endocrine organs, which secrete chemicals—the hormone—into the extracellular fluid. Hormones are transported primarily via the bloodstream throughout the body, where they bind to receptors on target cells, inducing a characteristic response. As a result, endocrine signaling requires more time than neural signaling to prompt a response in target cells, though the precise amount of time varies with different hormones.

The endocrine system includes the pituitary, thyroid, parathyroid, adrenal and pineal glands (Figure 14.1.1). Some of these glands have both endocrine and non-endocrine (exocrine) functions, for example, the pancreas contains cells that function in digestion as well as cells that secrete the hormones insulin and glucagon, which regulate blood glucose levels. The hypothalamus, thymus, heart, kidneys, stomach, small intestine, liver, skin, female ovaries and male testes are other organs that contain cells with endocrine function. Additionally, adipose tissue has long been known to produce hormones and recent research has shown that even bone tissue has endocrine functions.

Endocrine system

The Pituitary Gland and Hypothalamus

The hypothalamus–pituitary complex (Figure 14.3.1) can be thought of as the “command center” of the endocrine system. This complex secretes several hormones that directly produce responses in target tissues, as well as hormones that regulate the synthesis and secretion of hormones of other glands.

Figure 14.3.1. Hypothalamus–pituitary complex. The hypothalamus region lies inferior and anterior to the thalamus. It connects to the pituitary gland by the stalk-like infundibulum. The pituitary gland consists of an anterior and posterior lobe, with each lobe secreting different hormones in response to signals from the hypothalamus.

Major pituitary hormones 

Major pituitary hormones and their target organs are shown in Figure 14.3.5.

Adipose Tissue: Hormone-producing Activities

Adipose tissue produces and secretes several hormones involved in lipid metabolism and storage. One important example is leptin, a protein manufactured by adipose cells that circulates in amounts directly proportional to levels of body fat. Leptin is released in response to food consumption and acts by binding to brain neurons involved in energy intake and expenditure. Binding of leptin produces a feeling of satiety after a meal, thereby reducing appetite. It also appears that the binding of leptin to brain receptors triggers the sympathetic nervous system to regulate bone metabolism, increasing deposition of cortical bone. Adiponectin—another hormone synthesized by adipose cells—appears to reduce cellular insulin resistance and to protect blood vessels from inflammation and atherosclerosis. Its levels are lower in people who are obese and rise following weight loss.

Section 3: Obesity with a Focus of Its Biomedical Perspective

Talk Overview

Easy access to nutrients has contributed to the increase in obesity in the human population. But, what is obesity and why isn’t everybody fat? Dr. Stephen O’Rahilly provides a biomedical perspective of obesity, and evaluates which genes could potentially shift the balance towards obesity. As he explains, one becomes obese when the balance between energy intake and energy spent is shifted. Surprisingly, mutations that lead to obesity in humans aren’t in genes involved in metabolism and energy storage, but failure in satiety signals in the brain that result in people eating too much. The excess of energy intake over energy expenditure leads to obesity.

What is the consequence of obesity in human health? Physically, obesity can result in lower mobility and sleeping disorders. But, in humans, the link between obesity and metabolic diseases isn’t straightforward. For example, not everyone that’s obese becomes insulin resistant. As O’Rahilly explains, the probability of an obese individual to have a metabolic disease is linked to the capacity of adipose tissue to store the extra fat. Mutations that decrease fat storage in adipose tissue increase the chance of metabolic diseases, like insulin resistance, even when the person is not obese.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• describe the functions of insulin and glucagon.
• differentiate between type I and type II diabetes.
• identify the health consequences of persistent high-level glucose.
• summarize the risk factors for type II diabetes.
• identify the diagnostic tests for diabetes.
• recognize various life style change strategies for Type II diabetes prevention and management.

Content

Section 1: Functions of Insulin and Glucagon

The Endocrine Pancreas

The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach (Figure 14.9.1). Although it is primarily an exocrine gland, secreting a variety of digestive enzymes, the pancreas has an endocrine function. Its pancreatic islets—clusters of cells formerly known as the islets of Langerhans—secrete the hormones glucagon, insulin, somatostatin and pancreatic polypeptide (PP) among others.

Regulation of Blood Glucose Levels by Insulin and Glucagon

Glucose is required for cellular respiration and is the preferred fuel for all body cells. The body derives glucose from the breakdown of the carbohydrate-containing foods and drinks we consume. Glucose not immediately taken up by cells for fuel can be stored by the liver and muscles as glycogen or converted to triglycerides and stored in the adipose tissue. Hormones regulate both the storage and the utilization of glucose as required. Receptors located in the pancreas sense blood glucose levels, and subsequently the pancreatic cells secrete glucagon or insulin to maintain normal levels.

Glucagon

Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged labor or exercise (Figure 14.9.2). In response, the alpha cells of the pancreas secrete the hormone glucagon, which has several effects:

• It stimulates the liver to convert its stores of glycogen back into glucose. This response is known as glycogenolysis. The glucose is then released into the circulation for use by body cells.
• It stimulates the liver to take up amino acids from the blood and convert them into glucose. This response is known as gluconeogenesis.
• It stimulates lipolysis, the breakdown of stored triglycerides into free fatty acids and glycerol. Some of the free glycerol released into the bloodstream travels to the liver, which converts it into glucose. This is also a form of gluconeogenesis.

Taken together, these actions increase blood glucose levels. The activity of glucagon is regulated through a negative feedback mechanism; rising blood glucose levels inhibit further glucagon production and secretion.

Insulin

The primary function of insulin is to facilitate the uptake of glucose into body cells. Red blood cells, as well as cells of the brain, liver, kidneys, and the lining of the small intestine, do not have insulin receptors on their cell membranes and do not require insulin for glucose uptake. Although all other body cells do require insulin if they are to take glucose from the bloodstream, skeletal muscle cells and adipose cells are the primary targets of insulin.

The presence of food in the intestine triggers the release of gastrointestinal tract hormones such as glucose-dependent insulinotropic peptide (previously known as gastric inhibitory peptide). This is in turn the initial trigger for insulin production and secretion by the beta cells of the pancreas. Once nutrient absorption occurs, the resulting surge in blood glucose levels further stimulates insulin secretion.

Insulin also reduces blood glucose levels by stimulating glycolysis, the metabolism of glucose for generation of ATP. Moreover, it stimulates the liver to convert excess glucose into glycogen for storage, and it inhibits enzymes involved in glycogenolysis and gluconeogenesis. Finally, insulin promotes triglyceride and protein synthesis. The secretion of insulin is regulated through a negative feedback mechanism. As blood glucose levels decrease, further insulin release is inhibited. 

Section 2: Disorders of the Endocrine System: Diabetes Mellitus

Dysfunction of insulin production and secretion, as well as the target cells’ responsiveness to insulin, can lead to a condition called diabetes mellitus.

There are two main forms of diabetes mellitus. Type 1 diabetes is an autoimmune disease affecting the beta cells of the pancreas. Certain genes are recognized to increase susceptibility. The beta cells of people with type 1 diabetes do not produce insulin; thus, synthetic insulin must be administered by injection or infusion. This form of diabetes accounts for less than five percent of all diabetes cases. Type 2 diabetes accounts for approximately 95 percent of all cases. About 80 to 90 percent of people with type 2 diabetes are overweight or obese. In type 2 diabetes, cells become resistant to the effects of insulin. In response, the pancreas increases its insulin secretion, but over time, the beta cells become exhausted. In many cases, type 2 diabetes can be reversed by moderate weight loss, regular physical activity, and consumption of a healthy diet; however, if blood glucose levels cannot be controlled, the diabetic will eventually require insulin.

Two of the early manifestations of diabetes are excessive urination and excessive thirst. They demonstrate how the out-of-control levels of glucose in the blood affect kidney function. The kidneys are responsible for filtering glucose from the blood. Excessive blood glucose draws water into the urine, and as a result the person eliminates an abnormally large quantity of sweet urine. The use of body water to dilute the urine leaves the body dehydrated, and so the person is unusually and continually thirsty. The person may also experience persistent hunger because the body cells are unable to access the glucose in the bloodstream.

Over time, persistently high levels of glucose in the blood injure tissues throughout the body, especially those of the blood vessels and nerves. Inflammation and injury of the lining of arteries lead to atherosclerosis and an increased risk of heart attack and stroke. Damage to the microscopic blood vessels of the kidney impairs kidney function and can lead to kidney failure. Damage to blood vessels that serve the eyes can lead to blindness. Blood vessel damage also reduces circulation to the limbs, whereas nerve damage leads to a loss of sensation, called neuropathy, particularly in the hands and feet. Together, these changes increase the risk of injury, infection, and tissue death (necrosis), contributing to a high rate of toe, foot, and lower leg amputations in people with diabetes.

Uncontrolled diabetes can also lead to a dangerous form of metabolic acidosis called ketoacidosis. Deprived of glucose, cells increasingly rely on fat stores for fuel. However, in a glucose-deficient state, the liver is forced to use an alternative lipid metabolism pathway that results in the increased production of ketone bodies (or ketones), which are acidic. The build-up of ketones in the blood causes ketoacidosis, which—if left untreated—may lead to a life-threatening “diabetic coma.” Together, these complications make diabetes the seventh leading cause of death in the United States.

Diabetes is diagnosed when lab tests reveal that blood glucose concentrations are higher than normal, a condition called hyperglycemia.

The treatment of diabetes depends on the type, the severity of the condition, and the ability of the patient to make lifestyle changes. Research advances have resulted in alternative options, including medications that enhance pancreatic function.

Section 3: Risk Factors and Prevention of Type II Diabetes

Diabetes Risk Factors (CDC)

Type 1 diabetes is thought to be caused by an immune reaction (the body attacks itself by mistake).

Risk factors for type 1 diabetes are not as clear as for prediabetes and type 2 diabetes. Known risk factors include:

• Family history: Having a parent, brother, or sister with type 1 diabetes.
• Age: You can get type 1 diabetes at any age, but it usually develops in children, teens, or young adults.

In the United States, White people are more likely to develop type 1 diabetes than African American and Hispanic or Latino people.

Currently, no one knows how to prevent type 1 diabetes.

Known risk factors for type 2 diabetes:

• Have prediabetes. (a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as type 2 diabetes)
• Are overweight.
• Are 45 years or older.
• Have a parent, brother, or sister with type 2 diabetes.
• Are physically active less than 3 times a week.
• Have ever had gestational diabetes (diabetes during pregnancy) or given birth to a baby who weighed over 9 pounds.
• Are an African American, Hispanic or Latino, American Indian, or Alaska Native person. Some Pacific Islanders and Asian American people are also at higher risk.

If you have non-alcoholic fatty liver disease you may also be at risk for type 2 diabetes.

Ready to see where you stand? Take the 1-minute prediabetes risk test.

Prevention and Management of Type II diabetes:

Can Type 2 Diabetes Be Prevented? Yes! You can prevent or delay type 2 diabetes with proven, achievable lifestyle changes—such as losing a small amount of weight and getting more physically active—even if you’re at high risk.

Tests for Type 1 Diabetes, Type 2 Diabetes, and Prediabetes

• A1C Test: The A1C test (a simple blood test) measures your average blood sugar level over the past 2 or 3 months.
• Fasting Blood Sugar Test: This measures your blood sugar after an overnight fast (not eating).
• Glucose Tolerance Test: This measures your blood sugar before and after you drink a liquid that contains glucose. You’ll fast (not eat) overnight before the test and have your blood drawn to determine your fasting blood sugar level. Then you’ll drink the liquid and have your blood sugar level checked 1 hour, 2 hours, and possibly 3 hours afterward.
• Random Blood Sugar Test: This measures your blood sugar at the time you’re tested. You can take this test at any time and don’t need to fast (not eat) first. A blood sugar level of 200 mg/dL or higher indicates you have diabetes.

Knowledge Check

Learning Objectives:

By the end of this section, you will be able to:

• summarize the processes of urine formation.
• identify the functions of the kidney.
• describe the risk factors for CKD.
• identify the health consequences of CKD.
• name the diagnostic tests for CKD,
• summarize the treatment options for CKD.

Content

Section 1: Basics of Anatomy and Physiology of the Kidney

External Anatomy

In humans, the left kidney is located at about the T12 to L3 vertebrae, whereas the right is lower due to slight displacement by the liver. Upper portions of the kidneys are somewhat protected by the eleventh and twelfth ribs (Figure 17.3.1).

On the superior aspect of each kidney is the adrenal gland. The adrenal cortex directly influences renal function through the production of the hormone aldosterone to stimulate sodium reabsorption.

Nephrons and Vessels

Nephrons are the “functional units” of the kidney; they cleanse the blood and balance the constituents of the circulation. (Figure 17.3.3)

• Nephron: Renal Corpuscle + Renal Tubules
• Renal Circulation: Renal Artery → 2 Renal Capillary Networks (glomerulus and peritubular capillaries) → Renal veins

Urine Formation:

1. Glomerular Filtration: the movement of substances from the blood within the glomerulus into the capsular space (Bowman’s capsule)
   1. Freely filtered: Water glucose amino acids ions urea water soluble vitamins
   2. Not filtered regular cells white blood cells playlist large proteins
2. Tubular Reabsorption: the movement of substances from the tubular fluid back into the blood
   1. 100% of nutrients
   2. 100% of proteins
   3.  majority of water
   4.  majority of ions
3. Tubular Secretion: the movement of substances from the blood into the tubular fluid
   1. Some drugs
   2. Nitrogenous waste

The Urinary System and Homeostasis

All systems of the body are interrelated. A change in one system may affect all other systems in the body, with mild to devastating effects. A failure of urinary continence can be embarrassing and inconvenient but is not life threatening. The loss of other urinary functions may prove fatal.

Vitamin D Synthesis

In order for vitamin D to become active, it must undergo a hydroxylation reaction in the kidney. Activated vitamin D is important for absorption of Ca2+ in the digestive tract, its reabsorption in the kidney and the maintenance of normal serum concentrations of Ca2+ and phosphate. Calcium is vitally important in bone health, muscle contraction, hormone secretion, and neurotransmitter release.

Erythropoiesis

Erythropoietin, EPO stimulates the formation of red blood cells in the bone marrow. The kidney produces 85 percent of circulating EPO; the liver, the remainder.

Blood Pressure Regulation

Due to osmosis, water follows where Na+ leads. Much of the water the kidneys recover from the forming urine follows the reabsorption of Na+.

The kidneys cooperate with the lungs, liver and adrenal cortex through the renin–angiotensin–aldosterone system. The liver synthesizes and secretes the inactive precursor angiotensinogen. When the blood pressure is low, the kidney synthesizes and releases renin. Renin converts angiotensinogen into angiotensin I and ACE produced in the lung converts angiotensin I into biologically active angiotensin II (Figure 17.10.1). The immediate and short-term effect of angiotensin II is to raise blood pressure by causing widespread vasoconstriction. Angiotensin II also stimulates the adrenal cortex to release the steroid hormone aldosterone, which results in renal reabsorption of Na+ and its associated osmotic recovery of water. The reabsorption of Na+ helps to raise and maintain blood pressure over a longer term.

Regulation of Osmolarity

Blood pressure and osmolarity are regulated in a similar fashion.

Recovery of Electrolytes

Sodium, calcium and potassium must be closely regulated. Failure of K+ regulation can have serious consequences on nerve conduction, skeletal muscle function, and most significantly, on cardiac muscle contraction and rhythm.

pH Regulation

Enzymes lose their three-dimensional conformation and therefore their function, if the pH is too acidic or basic. Proper kidney function is essential for pH homeostasis.

Section 2: Chronic Kidney Disease (CKD)

CKD is a condition in which the kidneys are damaged and cannot filter blood as well as they should. Because of this, excess fluid and waste from blood remain in the body and may cause other health problems, such as heart disease and stroke.

Risk Factors:

Diabetes and high blood pressure are the more common causes of CKD in most adults. Other risk factors include heart disease, obesity, a family history of CKD, inherited kidney disorders, past damage to the kidneys, and older age.

Health consequences of CKD include:

• Anemia or low number of red blood cells
• Increased occurrence of infections
• Low calcium levels, high potassium levels, and high phosphorus levels in the blood
• Loss of appetite or eating less
• Depression or lower quality of life

Testing for KD

Urine Tests

One of the earliest signs of kidney disease is when protein leaks into your urine (called proteinuria).

• Dipstick urine test. This test is often done as part of an overall urinalysis, but it can also be done as a quick test to look for albumin (a protein produced by your liver) in your urine. It does not provide an exact measurement of albumin but does let your doctor know if your levels are normal. A dipstick (a chemically treated paper) is placed in a urine sample you provide and if levels are above normal, the dipstick changes color.
• Urine albumin-to-creatinine ratio (UACR). This test measures the amount of albumin and compares it to the amount of creatinine (a waste product that comes from the normal wear and tear of muscles in the body) in your urine. A UACR test lets the doctor know how much albumin passes into your urine over a 24-hour period. A urine albumin test result of 30 or above may mean kidney disease.

Blood Tests

Because your kidneys remove waste, toxins, and extra fluid from the blood, a doctor will also use a blood test to check your kidney function. The blood tests will show how well your kidneys are doing their job and how quickly the waste is being removed. Here are a few blood tests that are used:

• Serum creatinine. A serum creatinine blood test measures the amount of creatinine in your blood. If your kidneys are not working like they should, your serum creatinine level goes up. Normal levels for you will depend on your sex, age, and the amount of muscle mass your body has.
• Glomerular filtration rate (GFR). The GFR is a measure of how well your kidneys remove waste, toxins, and extra fluid from your blood. Your serum creatinine level, age, and sex are used to calculate your GFR number.
• Blood urea nitrogen (BUN). This test measures the amount of urea nitrogen in your blood. Urea nitrogen is a waste product your body makes from the breakdown of protein in the foods you eat. Healthy kidneys filter urea nitrogen out of your blood and it leaves your body through your urine. 

Stages of CKD: (See Table below)

• 5 stages
• Early Stages 1-3
• End Stage: kidneys no longer work as they should to meet your body's needs.

Symptoms and Treatment of CKD

Early stages of CKD

• Usually no symptoms. (because the body is usually able to cope with a significant reduction in kidney function)
• Kidney disease is often only diagnosed at this stage if a routine test for another condition, such as a blood or urine test, detects a possible problem.
• Treatment: medicine and regular tests to monitor it may help stop it becoming more advanced.

Later stages of CKD

• weight loss and poor appetite
• swollen ankles, feet or hands – as a result of water retention 
• shortness of breath
• tiredness
• blood in your pee (urine)
• an increased need to pee – particularly at night 
• Treatment: dialysis or kidney transplant

Dialysis

Knowledge Check