Download ENDOCRINE SYSTEM TOPICS

 ENDOCRINE SYSTEM TOPICS PART ONE: BASIC HORMONES PART TWO: HYPOTHALAMUS & PITUITARY GLAND 13.23 PART THREE: THYROID & PARATHYROID GLANDS 7:24 PART FOUR: ADRENAL GLAND & PANCREAS 10:04 PART FIVE: PINEAL GLAND & OTHER TISSUES 3:30 1
2:45 ENDOCRINE SYSTEM The endocrine system is made of various glands spread throughout the body. There are three glands in the brain, the hypothalamus, pituitary gland, and the pineal gland. The thyroid gland is in the neck. In the abdomen we can find the pancreas behind the stomach. On top of each kidney are the adrenal glands. In men the testes are part of the endocrine system, while in women, the ovaries are part of the endocrine system. There are a number of other hormone producing glands that are not a part of the endocrine system. Some of these hormone producing areas are the stomach, intestines, thymus, heart, fat, etc. These other tissues or organs will be discussed in greater detail in their own respective chapters. Hypothalamus Pineal Gland Pituitary Gland Thyroid Gland
Adrenal Glands Pancreas Ovaries (females)
Testes (males)
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HORMONE ACTION The endocrine system uses glands to release chemicals called hormones into the blood. These hormones travel throughout the entire body and will target any cell that has receptors for that hormone. Because hormones have effects on tissues all over the body, the action of that hormone depends on the membrane receptor and the target cell. Like testosterone increasing hair production from facial hair follicles or sperm production in the testes. Same hormone, different action depending on where the cell is and what that cell does. The nervous system and endocrine system are both communication systems within our body but they differ in a number of ways. The nervous system uses nerves instead of hormones. The nervous system is a ‘hardwired’ system like a land‐line telephone, it only communicates with what it is directly connected to. This allows the nervous system to be much faster than the endocrine system. The endocrine system takes minutes to hours to work while the nervous system is virtually instantaneous. Water‐Soluble Hormones Hormones are classified as either water soluble or lipid soluble. Water soluble hormones are protein‐
based and have receptors, like a docking station, that is on the surface of a cell membrane. These receptors have to be on the outside of a cell because water soluble hormones cannot cross the lipid bilayer that makes up the cell membrane. Once the hormone binds with the outer receptor, it starts a chemical cascade called a second messenger system which then causes something to happen inside the cell, usually release pre‐made proteins. Lipid‐Soluble Hormones Lipid soluble hormones are cholesterol‐based and can go right through the cell membrane to connect to receptors or docking stations inside the cell. Once the hormone binds to the receptor inside the cell, it can activate activity within the nucleus. Lipid soluble hormones must access DNA strands to create the new proteins, this takes longer than water soluble’s release of ready‐made proteins and the formation of new proteins have many implications in health and disease, specifically cancer. 3
HYPOTHALAMUS
The hypothalamus is located in the diencephalon, below the thalamus. The hypothalamus is one of the primary autonomic control centers of our body. This is how we maintain control over many of the function of our body that we ‘don’t have to think about’, like blood pressure, testosterone or estrogen production, sperm or egg Hypothalamus
development, thirst control, hunger cravings, metabolism, etc. In order to maintain homeostasis over so many Pituitary gland
Infundibulum different types of physiological processes, the hypothalamus receives many different types of information (blood pressure, hormone levels, electrolyte balance, etc). Once a particular parameter is considered to be ‘out of homeostasis or out of balance’, the hypothalamus then communicates with the pituitary gland to “fix the problem’ or carry out an action. What is important to understand is that the hypothalamus does not directly control any organ or tissue, it only controls the pituitary gland. The pituitary gland will then target the tissues or organs of the body. The hypothalamus is connected to the pituitary gland, by a thin connection called the infundibulum. The pituitary gland is located inferior to the hypothalamus and is encased within the sella turcica of the sphenoid bone. The pituitary gland is divided into two parts: anterior and posterior. The anterior pituitary is controlled by hormones released by the hypothalamus. The hormones from the hypothalamus to the anterior pituitary gland, travel through a two‐capillary bed network called the hypophyseal portal system, located within the infundibulum. There are two groups of hormones made by the hypothalamus to control the anterior pituitary gland. “Releasing" hormones travel to the anterior pituitary gland to initiate the release a particular hormone out to the body. "Inhibiting” hormones travel to the anterior pituitary gland to stop the release of a particular hormone. The posterior pituitary is controlled by nerves coming from the hypothalamus through the infundibulum. The nerves that control the posterior pituitary gland have cell bodies in the hypothalamus and axon terminals in the posterior pituitary gland. The action from the hypothalamus to the posterior pituitary gland involves direct nerve control. This causes chemicals from the neuron to be released in the posterior pituitary gland, then sent out to the body. Summary: Hypothalamus • • • • Located in the diencephalon Receives information from the body about autonomic functions Controls the pituitary gland to cause an effect on the body Pituitary control through two pathways: releasing or inhibiting hormones through the hypophyseal portal system and direct nerve control 4
PITUITARY GLAND The pituitary gland is located inferior to the hypothalamus, encased within the sella turcica of the sphenoid bone. It is connected to the hypothalamus by a ‘stalk’ called the infundibulum. The pituitary gland is also called the hypophysis which means “to grow beneath”. The pituitary gland has two distinct regions, anterior and posterior, both of which secrete hormones to the body. The posterior pituitary gland is also known as the “neurohypophysis” where neuro refers to the fact that it is made entirely of nerves and controlled by nerve impulses from the hypothalamus. This exemplifies the direct neural connection between the posterior pituitary and the hypothalamus. On a histology slide, the posterior pituitary gland has a more uniform or plain appearance in comparison to the anterior pituitary gland. There are two hormones released out to the body from this region of the pituitary gland: antidiuretic hormone and oxytocin. Posterior Pituitary Antidiuretic hormone targets the kidney tubules to retain water under conditions of dehydration or high solute or electrolyte concentration. The result of reduced water excretion is balanced electrolyte levels and increased blood volume. It acts as a “don’t pee” hormone. Oxytocin is a powerful hormone that targets smooth muscle, specifically the uterus and milk ducts in the breast. It stimulates uterine contraction during labor, stimulates milk ejection or “let down” of milk, and plays a role in orgasm in both men and women. Other actions of oxytocin are not well defined. 5
Anterior Pituitary The anterior pituitary gland is also known as the “adenohypophysis” where adeno means ‘gland’. It is controlled by hormones travelling from the hypothalamus through the hypophyseal portal system in the infundibulum. The anterior pituitary gland contains many different cells to produce about 6 different hormones. On a histology slide, you can see a number of color variations indicating the many different cell types. Thyroid stimulating hormone is released by the anterior pituitary and targets only the thyroid gland. The action on the thyroid gland is to release the thyroid hormones, T3 and T4, which increase metabolism, under normal conditions. The stimulus sequence begins with the hypothalamus detecting low metabolism. The hypothalamus then sends out thyrotropin releasing hormone to the anterior pituitary, which then sends out thyroid stimulating hormone. Thyroid stimulating hormone then circulates throughout the body to finally act on its target, the thyroid gland. Adrenocorticotropic hormone does what its name is. ‘Adreno’ indicates it is going to the adrenal gland, ‘cortico’ indicates it is going to the cortex or outer region of the adrenal gland and ‘tropic’ indicates that its target is specific to that area, nowhere else in the body. Once adrenocorticotropic hormone targets the adrenal cortex, it will release a family of hormones called glucocorticoids. Cortisol is the main stress hormone in this family that is released. This process begins when the hypothalamus detects a state of ‘stress’. The hypothalamus then sends out corticotropin releasing hormone through the hypophyseal portal system to the anterior pituitary. The anterior pituitary then sends out adrenocorticotropic hormone throughout the body targeting the adrenal cortex, which in turn releases cortisol (actions discussed in adrenal gland section). Luteinizing hormone is released by the anterior pituitary gland targeting the gonads stimulating the release of sex steroids. In women, luteinizing hormone targets the ovary to release of estrogen and a luteinizing hormone surge in mid‐cycle will cause an egg to be released. In men, luteinizing hormone targets the testes to increase testosterone production. The hypothalamus detects circulating testosterone and estrogen levels. When these levels are low, the hypothalamus sends gonadotropin releasing hormone through the hypophyseal portal system to the anterior pituitary gland. Luteinizing hormone is then released, targeting the gonads to increase sex steroid production. There are also a number of other hormones and reproductive factors that affect the hypothalamus control of this hormone that are beyond the scope of our course. Follicle stimulating hormone is released by the anterior pituitary gland targeting the gonads to stimulate gamete production. In women, follicle stimulating hormone targets the ovary to develop an egg for ovulation. In men, follicle stimulating hormone targets the testes to increase and support sperm production. The hypothalamus regulates the gamete production cycle, which vary considerably from male to female and will be discussed in greater detail in the reproductive system chapter. Prolactin is released by the anterior pituitary gland with receptors all over the body. Prolactin binding to receptors located on mammary glands (breast tissue) cause milk production in lactating women. Both men and women have prolactin, although the role of prolactin in men is not clearly defined. Although 6
there are prolactin receptors all over the body, the role of this complex hormone outside of milk production is poorly understood. Growth hormone is released by the anterior pituitary gland and targets tissues all over the body. Its primary purpose is for skeleton growth in children at the epiphyseal plates as well as musculature. It increases protein synthesis (as occurs with muscle or tissue building), increases lipid breakdown and mobilization of fatty acids, and affects on insulin and blood glucose levels. When the hypothalamus initiates the release of growth hormone from the anterior pituitary gland, it sends out growth hormone releasing hormone into the hypophyseal portal system. The pituitary gland then releases growth hormone. Deep sleep in children is associated with a surge of growth hormone release. Summary: Pituitary Gland • Located under the hypothalamus in the brain • Histological features: two distinct regions (anterior and posterior) • Anterior pituitary gland releases 6 hormone to know • Posterior pituitary gland releases 2 hormones 7
THYROID GLAND The thyroid gland is located on the anterior side of the neck. You can feel it under the skin, just below the Adams apple and between the sternocleidomastoid muscles. Lift your chin upward slightly to palpate the gland. The thyroid gland is shaped like a bow tie, with a narrow central region called the isthmus. On either side of the isthmus, the thyroid gland enlarges into a right lobe and a left lobe. When we look at a thin slice of the thyroid gland under a microscope under low power, we first notice a pattern of many circles. Looking more closely we can see dots surrounding the pink‐colored circles. Then at high power, it becomes more clear that the dots surrounding the circles are actually cells. You may see some red blood cells in the areas around the large pink circles, this is common as all glands have a lot of blood vessels within them to allow the hormones from those gland to readily enter the circulation. The large pink circular areas are called follicles. These follicles are filled with a large molecule called thyroglobulin which is a storage form for the thyroid hormones T3 and T4. Surrounding each follicle, are follicular cells. These are made of simple cuboidal epithelial tissue and are the target for thyroid stimulating hormone from the anterior pituitary gland. Thyroid stimulating hormone from the anterior pituitary gland targets these follicular cells to initiate the release of the thyroid hormones, T3 and T4 from within the follicles into the blood stream and out to the cells of the body. The cells in the areas outside of and adjacent to the follicles are called parafollicular cells. Parafollicular cells are also known as C cells because they produce the calcium hormone Calcitonin. Calcitonin is the third hormone produced by the thyroid gland. It is produced by the parafollicular cells located outside of the pink follicles. Calcitonin targets the bones of the skeletal system and the kidneys for calcium regulation. The role of calcitonin is to lower blood calcium levels. Calcitonin accomplishes this in two ways. Calcitonin targets the kidney tubules to excrete more calcium out into the urine and by targeting the bones to take up more calcium for storage. High blood calcium levels, not the pituitary gland, initiate the release of calcitonin from the thyroid gland. The main hormone produced by the thyroid gland is tetraiodothyronine most commonly called T4 or Thyroxine. The thyroid also produces triiodothyronine, commonly called T3. T3 is produced by the thyroid in much smaller quantities; however T3 is the more bioactive form that is preferred by the cells of the body. These hormones are made by the follicular cells and stored in the many large follicular pools found within the thyroid gland. 8
T3 and T4 from the follicular cells of the thyroid gland have an effect on all the cells of our body. Its primary function is related to lipid and carbohydrate metabolism and the basal metabolic rate. In children, T3 and T4 play a role in growth and brain development. The stimulus to release these thyroid hormones comes from thyroid stimulating hormone from the anterior pituitary gland. When the basal metabolic rate of the body has slowed down, it is detected by the hypothalamus, which sends thyrotropin releasing hormone to the anterior pituitary gland, then the anterior pituitary releases thyroid stimulating hormone to the thyroid gland, which in turn releases T3 and T4. T4 and T3 are each named for how many iodines they have attached. Tetraiodothyronine has four iodine molecules and triiodothyronine has three iodine molecules. T3 is the bioactive form that is most readily utilized by our bodies cells to increase mitochondrial metabolism. Since the thyroid gland makes mostly T4, and very little T3, each cell must take in the T4 and use an enzyme to cut off an iodine to make their own T3. Under normal conditions, the iodine that the enzyme removes makes T3 that increases metabolism. Recently it has been found that under stressful conditions, a different iodine molecule is removed which makes ‘ reverse T3’ causing a decrease in metabolism. This is an important finding because this explains what is going on in patients that have hypothyroid symptoms but have lab work indicating normal amounts of T3 and T4. Only recently have laboratories been able to test specifically for normal T3 and for reverse T3. Summary: Thyroid Gland • Located in the neck with a narrow central region and enlarges as it wraps around the airway • Histological features: circular pools called follicles, surrounded by follicular cells, with adjacent parafollicular cells • Releases two hormones that affect metabolism (T3 and T4) and calcitonin which decreases blood calcium levels • Pituitary control through two pathways: releasing or inhibiting hormones through the hypophyseal portal system and direct nerve control PARATHYROID GLAND There are four separate small glands located on the posterior surface of the thyroid gland called parathyroid glands. The main hormone produced by these glands is parathyroid hormone, produced by chief cells. Its role is to increase blood calcium levels. It is the most important regulator of calcium and phosphorus in the body. Parathyroid hormone targets the bones, kidneys, and intestines to increase blood calcium. Kidneys are stimulated to retain calcium, calcium is taken out of bones, and more calcium is absorbed from food by the intestines. All of this works together to increase blood calcium levels for use in a variety of chemical and physiological processes. Therefore, the stimulus to release parathyroid hormone is low blood calcium levels. 9
ADRENAL GLAND The adrenal gland is located inside the retroperitoneal cavity and sits on top of each kidney. The adrenal gland is two glands in one. The adrenal cortex is the outer region or “crust”. The adrenal medulla is the middle region. Think of the adrenal gland like a jelly donut, with the inner jelly part the ‘medulla’. Like the donut part of a jelly donut, the cortex portion goes all the way around. Adrenal Cortex The adrenal cortex has three distinct layers called zona. Starting from the outermost layer, there is the zona glomerulosa, zona fasciculata, and zona reticularis. The zona glomerulosa releases a family of hormones called mineralcorticoids. The main hormone from this family is aldosterone. Aldosterone acts on the kidney tubules to retain sodium and water which increases blood volume and can increase blood pressure. Aldosterone also increases potassium excretion via the urine. Mineralcorticoid release is stimulated by high extracellular potassium levels and a powerful blood pressure hormone called aldosterone II. The zona fasciculata releases a family of hormones called glucocorticoids. The most common is hydrocortisone, better known as cortisol. All cells in the body have Adrenal Cortex receptors for these hormones. The main effect is to increase fat use, conserve glucose by increasing formation but reducing use so blood glucose levels remain elevated. Adrenal Medulla In addition, cortisol can increase abdominal fat accumulation which has recently been shown to dramatically increase cardiovascular disease risk in a combination of factors called Metabolic Syndrome. There are known anti‐inflammatory effects, which is why a form of this hormone is used clinically as an anti‐inflammatory. Adrenocorticotropic hormone from the anterior pituitary gland is the main stimulus to release glucocortiocids. The process begins with the hypthalamus within the brain sensing stress (physiological like damage or psychological) and releases corticotropin releasing hormone through the hypophyseal portal system to the anterior pituitary. The anterior pituitary then sends out adrenocorticotropic hormone throughout the body targeting the zona fasciculata of the adrenal cortex. The zona reticularis secretes sex hormones, primarily androgens like testosterone. However, estrogen can also be made from this region. Testosterone increases male‐like secondary sex characteristics like increased muscle mass, and facial hair growth. This zona is stimulated to release hormones by circulating sex hormone levels. 10
Adrenal Medulla The adrenal medulla secretes the hormones of the sympathetic nervous system, epinephrine and norepinephrine. They target alpha and beta receptors, which have a multitude of functions all over the body. Their collective effects follow the “flight or fight” rule such as increased heart rate, pupil dilation, etc. Anything that will activate your autonomic nervous system sympathetic response like being scared will increase the release of these hormones. The release of these hormones allow our heightened physiological response to danger be sustained over a longer period of time. The example is when you get frightened you instantly feel the tightening of your stomach, this is the instantaneous nervous system effect. Then when you realize the danger was something like the wind and are no longer scared but your heart is still beating strongly for many minutes afterward, that is the sustained effect of the norepineprhine and epinephrine released as hormones. They take much longer to be removed from the circulation. Summary: Adrenal Gland • Located on top of the kidney, made of two different glands (adrenal cortex and adrenal medulla) • Histological features: cortex region wraps around medulla. Cortex contains three zona, medulla is just a group of cells in the center. • Adrenal cortex releases several groups of hormones from the three zona: mineralcorticoids from zona glomerulosa, glucocorticoids from zona fasiculata, and androgens and sex hormones from the zona reticularis. • Adrenal medulla releases two hormones of the sympathetic nervous system: epinephrine and norepinephrine. 11
PANCREAS The pancreas is located deep inside the abdominal cavity. It is hidden under and behind the stomach. When the stomach is removed you can see the long pancreas, with a head tucked next to the first turn of the duodenum or small intestine and a tapered tail next to the spleen. This location near the intestine allows it to easily secrete the digestive enzymes for food processing. Islet of Langerhans Acini When a slice of the pancreas is removed and stained it looks fairly uniform with variations of purple. Acini are the clusters exocrine glands that are stained purple. Pancreatic acini secrete digestive enzymes that go through the pancreatic duct into the small intestine or duodenum. These exocrine cells make up the majority of the pancreatic tissue .The few light pink or pale regions are called Islets of Langerhans; some areas are large and some are small. These Islets are the endocrine portion of the pancreas which contain alpha and beta cells that produce the hormones glucagon and insulin, respectively. These hormones affect blood glucose levels. Insulin is required by our cells to shuttle glucose inside. All cells use glucose to make ATP for energy, in order to get the glucose in, insulin is required. When blood glucose levels are high, like after a meal, insulin is released from the Islets of Langerhans into the blood to help move the absorbed glucose from the blood into cells. When the working cells have enough glucose to meet their immediate energy needs, insulin helps to store excess glucose. Short‐term storage regions like the liver, store the glucose as glycogen while fat is where we store glucose for long‐term storage. Between meals when blood glucose levels drop and we are hungry, glucagon is released by the pancreas. Glucagon allows glucose that has been stored to be released into the blood, thus increasing blood glucose levels. The increased glucose levels allow our cells to maintain energy until we eat again. Summary: Pancreas • Located in the abdominal cavity under the stomach • Histological features: dark pink acini exocrine glands secrete digestive enzymes, lighter regions called Islet of Langerhans endocrine cells release insulin and glucagon • Releases two hormones: insulin lowers blood glucose by increasing cell uptake, glucagon raises blood glucose by releasing glucagon from storage areas. 12
Negative‐Feedback Loop for Insulin 
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Negative‐Feedback Loop for Glucagon 
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Eat carbohydrate Absorbed as glucose Blood sugar levels increase, above normal levels Islet of Langerhan’s β‐cells release insulin Insulin attaches to receptors on cells to help each to cell take in glucose from the blood Insulin helps liver cells take ‘extra’ glucose and store it as glycogen for use later, between meals Blood sugar level drops, to normal β‐cells stop releasing insulin 
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Hungry (between meals) Blood sugar level drops, below normal Islet of Langerhan’s α‐cells release glucagon Glucagon stimulates liver to breakdown glycogen into glucose to be released into the blood Blood sugar levels increase, back to normal levels α‐cells stop releasing glucagon Type I Diabetes Mellitus Type I Diabetes Mellitus is an auto‐immune disease where the person's own immune system attacks the beta cells in the Islets of Langerhans. This reduces the amount of insulin that the pancreas can release. When blood glucose levels rise after a meal, the glucose cannot enter cells to be used for energy. These patients must inject insulin after every meal to facilitate glucose uptake into cells. If they don’t, blood glucose levels become very high while the cells are starving for glucose since it can't enter the cell without insulin. This condition has traditionally been called "Juvenile‐onset diabetes" as most patients are diagnosed when they are young. Type II Diabetes Mellitus Type II Diabetes Mellitus is due to the desensitization of insulin receptors due to chronically high blood glucose levels and over insulin production. This develops over several years of excessive glucose and therefore excessive insulin levels. Patients are required to decrease 'simple' carbohydrate intake (carbohydrates that break down quickly like sugar). In extreme cases patients must inject insulin because ‘extra’ insulin is needed for cells to operate the glucose shuttle system. The goal of any treatment is to reduce the glucose levels and insulin that the cells are exposed to in order to re‐sensitize the receptors so that they can operate properly. Exercise and diet are the best long‐term solutions for this problem. Exercise is even more effective at insulin receptor resensitization than any drug on the market. 13
PINEAL GLAND The pineal gland is located in the posterior region of the diencephalon as part of the epithalamus. The pineal gland is a light sensitive gland that secretes the hormone melatonin. When the gland senses decreasing light levels or darkness, it increases the release of melatonin. Melatonin affects the circadian rhythm or 24‐hour body clock regulating our sleep‐wake cycles. As cortisol levels decline in the evening when we become sleepy, melatonin levels increase. This relationship may explain why it is difficult for people to fall asleep when they are stressed and have high cortisol levels. In animals, melatonin plays a role in seasonal behavior such as mating or hibernation based on the seasonal changes in daylight exposure. Melatonin has antioxidant properties which can reduce free radicals in the brain as well as aid the immune system. Increased melatonin levels are associated with increased growth hormone secretion in children. Summary: Pineal Gland • Located in the posterior region of the diencephalon (can be seen between posterior cerebrum and cerebellum). • Pineal gland releases melatonin which regulates the sleep‐wake cycle. • Melatonin has been found to have effects on a number of other systems and functions, however these mechanisms are not yet clearly understood. 14
OTHER ENDOCRINE TISSUES When studying the endocrine system, it is important to know that hormone‐producing tissues are not limited to those glands that are classified as a part of the endocrine system. There are many other tissues or organs that release hormones while also performing other primary functions. A few of these tissues are described briefly. The intestines have a primary function of digesting food and absorbing nutrients. In these processes, hormones are released to control the rate of food entering the intestines by the stomach, hormones to control the release of bile from the gall bladder, hormones to control the release of digestive enzymes from the pancreas, and other control needs. The specific hormones will be discusses in the gastrointestinal chapter. The kidneys have a primary function of filtering our blood, but also releases three different hormones. The hormones of the kidney affect blood pressure, oxygen delivery by increasing red blood cell production, and calcium absorption from the gut. The heart is our main organ for propelling blood throughout our circulatory system. It also can release a hormone which will lower blood pressure. The thymus is an important organ of the immune system with hormones that regulate the development of cells that aid our immunity to foreign invaders. Adipose is fat storage but even fat can release hormones. Leptin is a hormone that affects the hypothalamus and plays a role with appetite. 15
ENDOCRINE SUMMARY P ART O NE : B ASIC H ORMONES 1. Describe the similarities and differences between the nervous and the endocrine systems. 
The nervous and endocrine systems both are means of cells communicating with other cells to cause an effect. 
The nervous system utilizes nerves which release neurotransmitters onto receptors on the surface of a specific cell. The time course of neuroactivation is very fast, within milliseconds. 
The endocrine system utilizes glands which release hormones into the blood to circulate throughout the entire systemic circulation. The target for the hormones are on the surface of cells with specific receptors for that hormone. They may be in specific areas of the body or all over. 2. What is the difference between endocrine and exocrine glands? 
Endocrine glands secrete their product into the blood to circulate through the systemic circulation. 
Exocrine glands secrete their product out through ducts to a specific place (surface or in a cavity). 3. Describe how hormones are classified as either water‐soluble or lipid‐soluble and give examples of both types. 
Water‐soluble hormones are amino acid derivatives or peptide hormones. They target receptors on the surface of cells, activating a second‐messenger system to elicit an action or the release of pre‐made proteins. o Example: insulin, melatonin, calcitonin, growth hormone 
Lipid‐soluble hormones must travel through the blood on a carrier protein. They are steroid hormones or eicosanoids. Lipid‐soluble hormones target receptors inside the cell, as they can easily cross the lipid bilayer of cell membranes. They cause activation within the nucleus to produce the production of new proteins. o Example: estrogen, progesterone, testosterone, cortisol, aldosterone 4. Describe how water‐soluble hormones interact with a cell to cause a specific outcome. 
Water‐soluble hormones target receptors on the surface of cells, activating a second‐
messenger system to elicit an action or the release of pre‐made proteins. 5. Describe how lipid‐soluble hormones interact with a cell to cause a specific outcome. 
Lipid‐soluble hormones target receptors inside the cell, as they can easily cross the lipid bilayer of cell membranes. They cause activation within the nucleus to produce the production of new proteins. 16
P ART T WO : H YPOTHALAMUS & P ITUITARY 1. Describe the location of the hypothalamus and its relationship to the pituitary gland. 
The hypothalamus is located within the diencephalon below the thalamus. The pituitary gland is located within the sella turcica. The hypothalamus and pituitary gland is connected to via a stalk called the infundibulum. 2. Describe the function of the hypothalamus. 
The hypothalamus monitors a myriad of functions throughout the body (thirst, electrolyte balance, hunger, cold, stress, reproductive cycle, sleep, etc.). To control or alter systemic physiological function, the hypothalamus communicates with the pituitary gland to send pituitary hormones targeting specific tissues. 3. Describe how the hypothalamus controls the adenohypophysis. 
The hypothalamus sends inhibiting or releasing hormones through the hypophyseal portal system to the adenohypophysis, anterior pituitary gland, to stimulate or inhibit specific pituitary hormone release. 4. Describe how the hypothalamus controls the neurohypophysis. 
The hypothalamus communicates directly with the neurohypophysis, posterior pituitary gland, via nerves and neurotransmitters to stimulate the release of antidiuretic hormone or oxytocin. 5. What are the hormones produced by the hypothalamus and what are their targets? 
The hypothalamus produces a number of releasing hormones and a number of inhibiting hormones that travel through the hypophyseal portal system to the adenohypophysis. 6. What are the hormones produced by the anterior pituitary gland? For each hormone, indicate its target and action. 
Thyroid stimulating hormone: Targets the follicular cells of the thyroid to stimulate the formation of tetraiodothyronine (T4 or thyroxine) and triiodothyronine (T3). 
Adrenocorticotropic hormone: Targets the zona fasciculata of the adrenal cortex to cause the release of glucocorticoids. 
Follicle‐stimulating hormone: Targets follicles in the ovary and Spermatogonia in the Seminiferous tubules in the testes. Stimulates gamete production (egg and sperm, respectively). 
Luteinizing hormone: Targets thecal cells in the ovary and Leidig cells in the testes to produce hormones (estrogen and testosterone, respectively). In females, a mid‐cycle surge stimulates ovum release from the ovary. 
Prolactin: Receptors are located all over the body with many unknown functions. The known function is to stimulate milk production in mammary glands. 
Growth hormone: targets all cells in the body, particularly the liver where it is converted into insulin growth factor‐1. It stimulates growth and increased metabolism. 
Melanocyte stimulating hormone: you don’t need to know this one. 17
7. What are the hormones produced by the posterior pituitary gland? For each hormone, indicate its target and action. 
Antidiuretic hormone: target is the distal convoluted tubules of the kidneys to cause the reabsorption of sodium and water. 
Oxytocin: many targets throughout the body. Uterus and milk ducts are some. Oxytocin stimulates uterine contractions during labor or orgasm, and milk ejection during lactation. 8. Describe the conditions associated with excessive growth hormone. 
Acromegaly is due to an excessive production of growth hormone during adulthood. Result is greater than normal growth in the soft tissues and flat bones. 9. Describe the condition associated with insufficient growth hormone. 
Pituitary dwarfism is due to an insufficient production of growth hormone during childhood growth. Result is less than normal growth. 10. Describe the condition associated with insufficient antidiuretic hormone. 
Diabetes insipidus is due to the lack of antidiuretic hormone from the neurohypophysis. This alters water conservation mechanisms in the body allowing the release of excessive amounts of water. P ART T HREE : T HYROID & P ARATHYROID 1. Describe the location of the thyroid and parathyroid glands. 
The thyroid gland is located in the neck, wrapping around the trachea.  The four glands are found on the posterior surface of the trachea, two on each side. 2. Name the hormones produced by the thyroid gland. For each hormone: (1) name the action of that hormone, (2) name the cell that produces that hormone, and (3) indicate what activates the release of that hormone. 
Tetraiodothyronine (T4 or thyroxine) o Targets mitochondria of all cells, it becomes activated when enzymes cleave off an iodine. It increases mitochondrial action (metabolism). o Produced by follicular cells. o The release is activated by the presence of thyroid stimulating hormone from the adenohypophysis. 
Triiodothyronine (T3) o Targets mitochondria of all cells. It can increase or decrease mitochondrial action (metabolism), depending on what iodine has been cleaved off. o Produced by follicular cells. o The release is activated by the presence of thyroid stimulating hormone from the adenohypophysis. 
Calcitonin 18
Targets bones and kidneys. In the bone it inhibits osteoclast activity and during youth it stimulates osteoblast activity. In the kidneys it increases calcium excretion. o Produced by parafollicular cells (C‐cells). o The release is activated by elevated calcium levels in the blood. 3. Name the hormones produced by the parathyroid thyroid glands. For each hormone: (1) name the action of that hormone, (2) name the cell that produces that hormone, and (3) indicate what activates the release of that hormone. o
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Parathyroid hormone o Targets bone, kidneys, and indirectly the GI tract. In the bone, it stimulates osteoclasts to increase calcium release and inhibits ostoblasts. In the kidneys, it increases the reabsorption of calcium. Also in the kidneys it stimulates another hormone, Calcitriol that increases calcium and phosphate absorption from the GI tract. o Produced by chief cells. o The release is activated by a reduction in blood calcium levels. 4. Describe the difference between normal T3 and reverse T3, including structure and action. 
Normal T3 activates the mitochondria to increase metabolism. It is formed by an iodine being removed from T4. 
Reverse T2 inhibits mitochondrial action, decreasing metabolism. It is formed by the removal of a different iodine component from T4 than for normal T3. This difference in structure causes a much different effect at the cellular level. 5. Describe the activation and inactivation process (negative feedback loop) for tetraiodothyronine. o Hypothalamus detects low metabolism o Hypothalamus releases thryotropin releasing hormone, targeting the anterior pituitary gland. o The anterior pituitary gland releases thyroid stimulating hormone targeting the follicular cells of the thyroid gland. o Thyroid gland releases T3 and T4. o T3 and T4 target cells all over the body to increase the mitochondrial activity and metabolism. o Hypothalamus detects normal metabolism activity o Hypothalamus releases thyrotropin inhibiting hormone to stop the release of thyroid stimulating hormone and subsequent activation of the thyroid gland. 6. Describe the activation and inactivation process (negative feedback loop) for calcitonin. o Parafollicular cells detect high blood calcium levels. o Parafollicular cells release calcitonin. o Calcitonin targets bone to uptake calcium and kidneys to excrete calcium. o Parafollicular cells detect normal blood calcium levels. o Parafollicular cells stop the release of calcitonin. 19
P ART F OUR : A DRENAL G LAND & P ANCREAS 1. Describe the location of the adrenal cortex and the zona. 
The adrenal cortex surrounds the medulla. It is made of three layers called zona. Each zona secretes a particular group of hormones. 2. Describe the location of the adrenal medulla. 
The adrenal medulla is the inner core of the adrenal gland. It is made of modified nervous tissue so it releases norepinephrine and epinephrine into the blood. 3. Describe the location of the pancreas and the endocrine regions of the pancreas. 
The pancreas is located inferior to the stomach. The pancreas is primarily made of acini that release digestive enzymes into the small intestine (duodenum). There are small regions called the Islets of Langerhans that release the hormones glucagon and insulin that are released in response to low or high levels of blood glucose, respectively. 4. List the 3 zona of the adrenal cortex. For each zona: (1) name the group of type of hormone that is produced, (2) name a specific hormone, and (3) indicate the action of that hormone. 
Zona glomerulosa o Mineral corticoids o Aldosterone o Increased sodium retention and water retention by the kidneys 
Zona fasciculata o Glucocorticoids o Corticosterone, cortisol o Anti‐inflammatory effects, altered glucose utilization 
Zona reticularis o Androgens and sex hormones o Estrogen, testosterone o Activate secondary sex characteristics (body hair growth, , etc.) 5. Name the hormones produced by the adrenal medulla and describe what those hormones do. 
Norepinephrine and epinephrine mimic the effects of the sympathetic nervous system allowing stimulation over a longer time course than via the nervous system alone. 6. Describe a negative feedback loop for activation and inactivation of the zona glomerulosa. 
Low blood pressure 
Increased release of aldosterone 
Increased sodium reabsorption and water reabsorption by kidneys so blood volume is increased 
Blood pressure returns to normal  Inhibition of aldosterone release 7. What is the exocrine function of the pancreas? 
The pancreatic acini makes enzymes that digest carbohydrates, fats, and proteins. These enzymes are secreted in to the duodenum of the small intestine. 8. Name the endocrine region of the pancreas and the hormones produced by that region. 20

The islet of Langerhan’s produce glucagon and insulin. o Glucagon comes from alpha cells that increase the breakdown of glycogen stores, increasing blood glucose levels (between meals). o Insulin comes from beta cells that increase the cellular uptake of glucose, decreasing blood glucose levels. This is important immediately after a meal has been consumed. 9. Describe Type I diabetes. 
Type I diabetes occurs when the immune system targets beta cells for destruction causing the impairment of insulin production. People with type I diabetes must inject an appropriate amount of insulin after every meal to help the cells take in glucose for energy. 10. Describe Type II diabetes. 
Type II diabetes occurs after many years of excessive insulin production due to excessive and chronic high blood glucose levels. The high insulin production over many years causes the insulin receptors on the cells to become desensitized to insulin so the beta cells must produce more insulin than it normally needed to in order to get the cells to take in the glucose. o Treatment is to decrease the high glucose levels in the body and resensitize the insulin receptors so the body does not have to make so much insulin to get the job done. Exercise is the best receptor resensitizing treatment you can do because it tells the cells that glucose is needed for energy. Drugs available that also resensitize insulin receptors but none can do it to the level that basic exercise can. o In serious cases, insulin injections may be needed because the insulin receptors are so desensitized that the body can’t produce enough insulin to get the glucose into the cells so additional insulin is needed to keep the person alive. Ideally that person needs to get their insulin receptors resensitized as soon as possible because doing insulin injections is not curing the problem at all, it is actually perpetuating the problem. P ART F IVE : P INEAL G LAND & O THER T ISSUES 1. Describe the location of the pineal gland. 
The epithalamus in the diencephalon, above the thalamus. The largest portion is found on the posterior surface of the diencephalon above the corpora quadrigemina. 2. Describe the hormone produced by the pineal gland and what that hormone does. 
Melatonin release is activated by the absence of light. It facilitates sleep‐wake patterns and plays a primary role in seasonal behaviors and hormone production seen in animals (hibernation, mating, increased hair growth for winter before the temperature drops, etc.). In humans it plays a major role in coordinating many hormone release patterns. 21
3. Provide a list of other organs that have endocrine functions (but have other primary functions) and a hormone that they produce. 
Intestines: digestive regulatory hormones 
Kidneys: renin for blood pressure, erythropoietin for red blood cell production, and calcitriol for calcium absorption. 
Heart: atrial natriuretic peptide for blood pressure reduction 
Thymus: immune system hormones for the specific defenses 
Adipose tissue: leptin for hunger and satiety 22
ENDOCRINE STUDY ACTIVITIES EXERCISE 1: HORMONES For each hormone listed, please indicate the gland and specific region or cells the hormone comes from, and the action of that hormone. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 HORMONE Oxytocin Antidiuretic Hormone Thyroid stimulating hormone Adrenocorticotropic hormone Luteinizing hormone Follicle stimulating hormone Prolactin Growth hormone T3/T4 Calcitonin Parathyroid hormone Aldosterone Cortisol Androgens & sex hormones Epinephrine & Norepinephrine Insulin Glucagon Melatonin GLAND Pituitary REGION OR CELLS Posterior ACTION Smooth muscle contractions Men:
Women: Men:
Women: 23
EXERCISE 2: HISTOLOGY For each histology image, indicate the gland that image comes from and the cells or regions indicated. Gland. _______________
List the hormones produced by region B. List the hormones produced by region A. A. __________
B. ______
Gland. _______________
List the hormones produced by cells indicated in B. A. _____________cells (circled in red) List the hormone produced by cells indicated by the red circles. B. ________cells
Gland. _______________
List the hormones produced by region B. List the 3 classes of hormones produced by region A. A. _____________
B. ___________
Gland. _______________
A. _________________ List the hormones produced by cells indicated in A. What is produced by region B? A
B. ___________
24
EXERCISE 3: BRAIN GLANDS Please label and color the regions indicated. Pineal Gland Hypothalamus Adenohypophysis Neurohyophysis Hypophyseal Portal System 25
EXERCISE 4: THYROID & PARATHYROID ANATOMY Please label and color the regions indicated. anterior posterior Thyroid Gland Parathyroid Glands (4) Histology image from thyroid gland 26
Follicular Cells (Thyroid Gland)
Hormone produced:___________ Para follicular Cells (Thyroid Gland)
Hormone produced:___________ EXERCISE 5: PANCREAS ANATOMY Please label and color the regions indicated. Pancreas
Islet of Langerhans Hormone produced:___________ Hormone produced:___________ 27
Acini
Products produced:___________ Exercise 6: Adrenal Gland Anatomy Please label and color the regions indicated. Zona Glomerulosa
Hormone family or group produced: ____________________________________ Name one of those hormones:___________ Zona Fasciculata
Hormone family or group produced: ____________________________________ Name one of those hormones:___________ Zona Reticularis
Hormone family or group produced: ____________________________________ Name one of those hormones:___________ Adrenal Medulla
Hormones produced (2): ____________________________________ ____________________________________ 28
ENDOCRINE STUDY QUESTIONS THESE QUESTIONS ARE INTENDED TO GUIDE YOU TOWARD A DETAIL AND EMPHASIS IN STUDYING BY TRYING TO HELP CONNECT SEVERAL CONCEPTS TOGETHER. IT IS IMPORTANT TO FIND THE RIGHT ANSWER(S), AS WELL AS KNOW WHY THE WRONG ANSWERS ARE INCORRECT. 1.
2.
3.
4.
One benefit that water soluble hormones have over lipid soluble hormones is that__________. a. they have an ability to transverse the cell membrane b. they are slower and longer acting c. they activate pre‐made proteins, thus are “quicker” to end result d. they act in a more local area e. All of the above Which of the following statements is true? May be more than one. a. Pancreatic hormones can activate the activity in a cell’s nucleus b. Steroid hormones have direct action and receptors inside the cell c. Thyroid stimulating hormone activates the release of other hormones d. Sex‐hormones use a cAMP 2nd messenger system Which gland produces “inhibiting” or “releasing” hormones that do not travel all over the body? a. Pituitary gland b. Neurohypophysis c. Hypothalamus d. Adenohypophysis e. Adrenal gland Which hormones does the adenohypophysis (anterior pituitary) release? a. Antidiuretic hormone b. Thyroid‐stimulating hormone c. Releasing hormones d. Adrenocorticotropic hormone e. Luteinizing hormone f. Inhibiting hormones g. Prolactin h. Oxytocin i. Growth hormones j. Follicle stimulating hormones 29
5.
6.
7.
8.
Which hormones does the posterior pituitary or neurohypophysis release? a. Antidiuretic hormone b. Thyroid‐stimulating hormone c. Releasing hormones d. Adrenocorticotropic hormone e. Luteinizing hormone f. Inhibiting hormones g. Prolactin h. Oxytocin i. Growth hormones j. Follicle stimulating hormones Which hormones does the hypothalamus create and release? a. Antidiuretic hormone b. Thyroid‐stimulating hormone c. Releasing hormones d. Adrenocorticotropic hormone e. Luteinizing hormone f. Inhibiting hormones g. Prolactin h. Oxytocin i. Growth hormones j. Follicle stimulating hormone What hormone has the effect of releasing glucocorticoids? a. Oxytocin b. Luteinizing Hormone c. Growth hormone d. Adrenocorticotropic hormone e. Tetraiodothyronine Lutenizing hormone __________. a. is produced in the gonads b. causes gametes to be released from an ovary c. stimulates sperm and egg maturation d. stimulates the production of testosterone e. A, B, and C are correct f. B and D are correct 30
9.
10.
11.
12.
13.
Follicular cells__________. a. are cells found between follicles that produce calcitonin b. produce both T4 and T3 c. are simple cuboidal cells arranged in a circle in the thyroid d. are targeted by thyroid stimulating hormone from anterior pituitary e. B, C and D is correct f. All of the above are correct What hormone is increased by stress and decreases metabolism? a. Tetraiodothyronine or T4 b. Reverse triiodothyronine or rT3 c. Normal triiodothyronine or T3 d. Aldosterone e. Glucagon Which of the following is true? a. Triiodothyronine or T3 is also called Thyroxine b. Calcitonin is a hormone from the thyroid that lowers blood calcium levels c. Thyroid stimulating hormone has the greatest cellular effect on the mitochondria of cells in the body d. Calcitonin is increased by thyroxine After the hypothalamus detects low metabolism and stimulates the adenohypophysis with thyrotropin releasing hormone the __________. a. posterior pituitary releases thyrotropin b. thyroid releases T3 and T4 to increase metabolism of cells c. thyroid is stimulated by the thyroid stimulating hormone d. posterior pituitary releases thyroid stimulating hormone (TSH) Which of the following is a true statement regarding the adrenal cortex? a. Cortisol is a glucocorticoids that is produced in the zona reticularis. b. Corticosterone and cortisol are produced in the zona glomerulosa. c. Mineralcorticoids like aldosterone alter the concentration of electrolytes in the blood (which affects blood pressure). d. Testosterone is produced in the zona glomerulosa. 31
14.
15.
16.
17.
18.
The pancreas___________. a. releases glucagon from alpha cells which stimulates cells of the body to use blood glucose b. uses the majority of its tissue for exocrine (digestive enzyme) functions c. release insulin which helps the liver take in glucose from the blood for later use (storage) The pineal gland__________. a. has light receptors which help with sleep and seasonal regulation b. is in the posterior area of the brain and is superior to the epithalamus c. releases melatonin which helps to coordinate other hormone release patterns d. All are correct e. Only A and C are correct Which of the following hormones have a specific target in the body (i.e. only has an action on one organ, not on cells all over the body)? a. Thyroid stimulating hormone b. Cortisol c. Insulin d. Tetraiodothyronine e. Norepinephrine Which of the following organs has both an exocrine and endocrine function? a. Pituitary gland b. Pineal gland c. Adrenal gland d. Pancreas e. Thyroid gland What do ‘beta cells’ produce? a. Insulin b. Glucagon c. Melatonin d. Cortisol e. None of the above 32
19.
Thyroid stimulating hormone activates the production of _____________________ and _______________________, made by __________________________ cells. 20.
The zona fasiculata produces _________________. This hormone stimulated increased _________________ use, decreased ________________ use, and also has ______________ effects. It is activated by the __________________ hormone; examples are: _____________________ (stress hormone). 21.
_________________ activate sex hormones. _______________ and _____________ are examples of sex hormones. 22.
The pancreas contains __________________ and ________________ cells. The beta cells produce ____________, which ___________ blood glucose, and promotes glucose storage in the ________. It is secreted _________ meals. Glucagon is produced by ____________ cells; this ___________ blood glucose levels by ______________ glucose from storage areas. It is secreted ___________ meals. 23.
The pineal gland produces ___________________, which is affected by ________________. It regulates hormone secretion; additionally, it is a free radical scavenger in the ___________, and it also is related to sleep‐wake __________. 33
ENDOCRINE TERMS BASIC HORMONES ADRENAL GLAND & PANCREAS Endocrine System (vs. Nervous System) Hormones Receptors Water Soluble Hormones Lipid Soluble Hormones Adrenal Gland Adrenal Cortex Adrenal Medulla Zona glomerulosa Mineralcorticoids Aldosterone Zona fasciculata Glucocorticoids Cortisol Zona reticularis Androgens/Sex hormones Norepinephrine Epinephrine Sympathetic Nervous System Adrenocorticotropic Hormone Pancreas Acini cells Islet of Langerhans Alpha Cells Beta Cells Insulin Glucagon Glycogen Diabetes Mellitus (Type I) Diabetes Mellitus (Type II) Simple Carbohydrates Complex Carbohydrates HYPOTHALAMUS & PITUITARY Hypothalamus Pituitary Gland (hypophysis) Posterior Pituitary Gland (neurohypophysis) Anterior Pituitary Gland (adenohypophysis) Hypophyseal Portal System Releasing Hormones Inhibiting Hormones Antidiuretic Hormone Oxytocin Thyroid‐stimulating Hormone Tropic Hormone Adrenocorticotropic Hormone Follicle‐stimulating Hormone (female vs. male) Luteinizing Hormone (female vs. male) Prolactin Growth Hormone THYROID & PARATHYROID GLANDS Thyroid Gland Follicle Colloid (Thyroglobulin) Follicular Cells Parafollicular Cells Tetraiodothyronine (T4 or Thyroxine) Triiodothyronine (T3) Reverse T3 Calcitonin Parathyroid Glands Chief Cells Oxyphil Cells PINEAL GLAND & OTHER REGIONS Pineal gland Melatonin Intestines Kidney Renin Erythropoietin Calcitriol Atrial natriuretic peptide Thymus Adipose tissue Leptin 34
35
36
HEART TOPICS PART ONE: EXTERNAL HEART ANATOMY 8:53 PART TWO: INTERNAL HEART ANATOMY 14:38 PART THREE: ELECTRICAL CONDUCTION 21:50 PART FOUR: CARDIAC CYCLE & CARDIAC OUTPUT 37
12:03 HEART EXTERNAL CARDIAC ANATOMY The heart is located beneath the sternum inside the rib cage. The apex is the pointy inferior portion. It tips down and leftward and is located in the 5th intercostal space, between the 5th and 6th ribs. The base is the top part of the heart where the vessels enter/exit, located below the 2nd rib. The heart is a pump that propels blood through two different circulatory circuits at the same time. The first circuit is the pulmonary circulation which is specific to the lungs. The heart pumps blood to the lungs to get the blood oxygenated. The second circuit is the system circulation which is the rest of the body from the brain to the toes and all the organs in between. Vessels that extend from the heart are either arteries or veins. Arteries are considered to be high pressure because they receive the blood as it is being ejected from the heart, so arteries carry blood away from the heart and out to the body’s capillary beds. Veins are considered to be low pressure because they are returning blood back to the heart. Superficial Features The pericardium is a membrane that surrounds the heart containing the heart in its own space called the pericardial cavity. The membrane is a double membrane folded back on itself like a fist pushing into an inflated balloon. The part of the membrane that is touching the heart (or layer of balloon touching the fist in the example) is the visceral pericardium, while the outer layer that you can see is the parietal pericardium. In reality, it only looks like one layer, which is the parietal pericardium as the visceral pericardium is fused with the surface of the heart. On the surface of the heart you will first notice the pulmonary artery as the most anterior of the great vessels, and running diagonally. The aorta is immediately behind the pulmonary artery. The superior vena cava is a thin‐
walled vein that brings blood from the head and arms back to the heart. The inferior vena cava is also a thin‐walled vein that brings blood into the heart from the lower body and lower torso. On the upper surface of the heart you should notice two flap‐like structures, called auricles. These auricles are the upper regions of the right and left atria. 38
Muscular Layers The heart muscle is very thick. It is divided into three distinct layers. The outer layer is called the epicardium and it is fused with the visceral pericardium. When you see a slice out of a heart you can see this very thin outer layer is a little different from the ‘meaty’ muscular middle layer called the myocardium. Most of the heart wall is made of myocardium, this is the working part of the heart. The innermost layer that is in contact with the blood is called the endocardium. This layer lines the inside of the ventricles. Coronary Circulation Coronary arteries are the vessels that are found on the surface of the heart that deliver blood to the heart muscle itself. It is blockage of these arteries that cause a heart attack. The coronary arteries are surrounded by a fat pad covering as they sit in shallow ditches called a sulcus. This prevents the coronary arteries from being compressed from the outside when the heart expands inside the pericardial sac while it is filling with blood. The word “coronary” refers to a “crown”. This is because the coronary arteries form a circle around the upper region of the heart, with smaller arteries extending from it. The right and left main coronary arteries are the first branch off the aorta so the heart ‘feeds itself first’. The right coronary artery circles around the right side with a large branch coming off of it on the side, called the marginal branch and then to the back side to the posterior descending branch which serves the apex. The left main coronary artery is only a few millimeters long then it splits into two separate branches. The left anterior descending artery travels anteriorly and down the front middle surface of the heart. The left anterior descending artery has been recently referred to in recent textbooks as the ‘anterior interventricular artery’, however this name is not commonly used among cardiologist or the American Heart Association. The other branch that the left main coronary artery divided into is called the left circumflex artery. This one travels around the side to serve the lateral and posterior sides of the left side of the heart. It is important to note that the coronary arteries supplying oxygen to the heart only contain blood when the heart is at rest, known as diastole. This is because, at rest, the myocardium is not stiff and contracting and closing off vessels. Also during diastole, the flow of blood from the aorta to the coronary arteries is not blocked by the aortic valve. The many cardiac veins that drain the ‘used’ blood must return that blood to the heart so it can send it to the lungs for oxygenation again. All the cardiac veins drain their blood into a large, wide vessel like area called the coronary sinus. The coronary sinus then has a direct drainage hole into the right atrium where it returns to the regular circulation. 39
INTERNAL CARDIAC ANATOMY Inside the heart are four chambers or spaces for blood to go. The two smaller upper chambers are called atria and the two lower, larger chambers that actually propel the blood forward are called ventricles. Blood flows from the atria to the ventricles. Blood then goes from the ventricles out of the heart to the lungs or body. Valves are inside the heart to control the direction of flow through the heart. ATRIA In the upper region of the heart are two atrial chambers side‐by‐side with the interatrial septum separating them. Inside the atria it is smooth on the posterior surface, but the anterior region and in the auricles it has a comb‐like pattern of parallel ridges called musculi pectinati. The word comes from ‘pectin’ meaning comb. The purpose of the atria is first to allow blood to go through on the way to fill the ventricles below. When the contraction phase begins, it starts with both atria contracting first, pushing the last little bit of blood through and topping off the ventricles. In elderly hearts, the amount of blood that the atrial contraction adds to the ventricular filling becomes much more significant so anything that may compromise the action of the atria is not that problematic in young, healthy people but in elderly individuals it could reduce the amount of blood filled by the ventricles and therefore minimize ejection. Right Atrium The right atrium is the first place that blood returning to the heart from the body arrives at. The superior vena cava brings blood from the head and upper body to the right atrium. The inferior vena cava brings blood from the lower body to the right atrium. The blood that arrives at the right atrium is deoxygenated or ‘used up’ blood. In addition to the superior and inferior vena cava bringing blood from the body to the right atrium, there is also a hole where the coronary sinus drains into which contains the used up blood from the heart itself. Another unique feature found inside the right atrium is the fossa ovalis. The fossa ovalis is a circular indentation in the interatrial septum. In a fetus, this is the location of an actual hole called the foramen ovale (meaning “oval hole”) where blood would go through to bypass the right ventricle and lungs and go directly to the left atrium. At birth a flap then covers this hole and seals up, what remains is a slight indentation that we see as the fossa ovalis. Left Atrium The left atrium is the first place that blood returning from the lungs enters the heart. There are four pulmonary veins that create holes in the left atrium for the freshly oxygenated blood to enter, two from each lung. This oxygenated blood is now ready to be sent to the left ventricle to be ejected and distributed throughout the body. 40
VENTRICLES There are two ventricles. The right ventricle ejects deoxygenated blood into the pulmonary circulation. The left ventricle ejects oxygenated blood out to the body throughout the systemic circulation. The myocardium in the free wall on the left side of the heart is much thicker than the free wall on the right side. This is due to the higher pressures required by the left ventricle to squeeze and push blood throughout the systemic circulation compared to the right ventricle squeezing blood out to the lungs, which have very low pressures. The inside of the ventricles have a muscular pattern that cris‐cross like mesh or a net, this is called trabeculae carneae. The whole purpose of the heart is to provide the energy to the blood to propel it forward and keep the circulation moving, which is the primary function of the ventricles. Right Ventricle The right ventricle receives the body’s deoxygenated blood from the right atrium. It collects and fills until the heart begins the next contraction cycle or beat. When the heart contracts, the right ventricle ejects blood out to the lungs. The features that can be viewed when you look inside the right ventricle is first the myocardium on the free wall is thin compared to the left side. The right atrioventricular valve, more commonly known as the tricuspid valve, has strings to keep it in place called chordae tendinae which are attached to cone‐shaped myocardium pieces called papillary muscles. The pulmonary semilunar valve can also be seen in the outflow tract of the right ventricle. Left Ventricle The left ventricle receives the lung’s oxygenated blood from the left atrium. It collects and fills until the heart begins the next contraction cycle or beat. When the heart contracts, the left ventricle ejects blood out to the body. This takes a considerable amount of force so the heart wall on the left is much thicker, compared to the right ventricle. In people with high blood pressure, the heart wall has to get even thicker still, which can compromise chamber size. Inside the left ventricle, you can see the left atrioventricular valve, more commonly known as the mitral valve or bicuspid valve because it has two flaps. Like the tricuspid valve, it has strings to keep it in place called chordae tendinae which are attached to papillary muscles. The aortic semilunar valve can be seen in the outflow tract of the left ventricle. 41
VALVES Maintaining forward flow (preventing backflow) through the heart are four valves. The valves function using the pressure changes within the heart during a contraction‐relaxation cycle. Atrioventricular Valves Atrioventricular valves are just that. They are found inside the heart between the atria and the ventricles. There are two of them. One on the right side between the right atrium and the right ventricle and one on the left side between the left atrium and the left ventricle. These valves let blood into the ventricles, but prevent blood from going back that way when the ventricle is squeezing tightly during the contraction phase. Atrioventricular valves have large triangular flaps with strings called chordae tendinae attached to the papillary muscles. These valves allow blood to enter the ventricles, then when the ventricles contract and build pressure, the blood then billows up the valve flaps and the papillary muscles then pull on the chordae tendinae to hold the flaps in place like the chords on a parachute, this keeps the flaps from inverting, and keeps the blood from going back into the atria. The right atrioventricular valve is made of three flaps, which is why it is primarily called the tricuspid valve. The left atrioventricular valve is made of two larger flaps. It is most commonly called the mitral valve, but is also called the bicuspid valve. Semilunar Valves The other two valves are semilunar valve. These valve have very different features and they are located in the ventricular outflow tract at the base of both major arteries. There are three thin and strong cusps that make‐up these valves. The valves open easily when the ventricle ejects blood out into the arteries, pushing the cusps aside. Then, when the pressure in the ventricles decline during relaxation the blood then slows down and fill the cusps sealing them together, preventing backflow into the ventricles and maintaining forward flow. The pulmonary semilunar valve allows blood being ejected by the right ventricle to go out into the pulmonary trunk and then out to the lungs. As the right ventricle relaxes, the drop in pressure causes the blood in this region to fill the cusps and seal the valve shut so that no blood will go backward into the ventricle. The aortic semilunar valve allows the blood to leave the left ventricle as it is ejected from the heart and out to the body. During ventricular relaxation, the valve shuts by the weight of the blood as it fills the cusps. 42
Heart Sounds When you listen to your heart with a stethoscope you should hear a ‘double thump’. Instead of ‘thump, thump, thump..., you should heart lub‐dub, lub‐dub, lub‐dub. The sounds you hear are the valves shutting like a door slamming. The movement of blood should be silent. In a normal heart, you should only hear the valves close. Murmurs in the heart can be detected when you hear ‘swishing’. The first sound (lub) is the closing of both the right and left atrioventricular valves and the second heart sound (dub) are the pulmonary and aortic semilunar valves closing. Because of the position of the heart within the rib cage, you have to be careful about where you place the stethoscope to hear specific valve. Position the stethoscope up high in the second intercostal space to hear the semilunar valves. On the right side you can hear aortic semilunar valve as that is best positioned near the aortic arch. On the left side you can hear the pulmonary semilunar valve. This may seem backward but you have to consider the anatomical position of the pulmonary trunk and aorta for this to make sense. The tricuspid valve can be heart on the left side of the sternum in the 4th or 5th intercostal space. In the 5th intercostal space along the midclavicular line you can hear the mitral valve. PATHWAY OF BLOOD FLOW 1. Blood enters the atria and flows through to the ventricles. On the right side, deoxygenated blood enter the right atrium, crossing the tricuspid valve to the right ventricle. On the left side, oxygenated blood enters the left atrium, crossing the mitral valve to the left ventricle. 2. The ventricles get topped off with blood by atrial contraction. 3. The ventricles begin to contract, closing the atrioventricular valves (lub). The ventricles continue to squeeze, with blood going nowhere (isovolumic), as the semilunar valves are still closed. 4. Blood is ejected out through the open semilunar valves. The ventricles have reached the diastolic pressure in the aorta (for the left) and pulmonary artery (for the right). 5. Ventricular relaxation closes semilunar valves, but pressure has not dropped enough yet to open the atrioventricular valves and let the atrial blood in, so no volume change (isovolumic). 1 2 3
43
4
5 ELECTRICAL CONDUCTION Electrophysiology is the study of the electrical signals from the heart. All of the myocardial cells within the heart are electrically active and linked together. When a signal arises from an area, it will immediately activate surrounding cardiomyocytes in a wave‐like manner. There is a specific sequence that the electrical activity occurs, so that the contraction that follows will happen in a proper order. Conduction Pathway Although all the cardiomyocytes in the heart are capable of receiving and conducting electrical impulses, there are specific regions that are more electrically sensitive. These regions, are part of the conducting system, can self‐generate an action potential. The ability to create an action potential or electrical impulse independently, without innervation is why heart transplant patients have hearts that function without having the nerves reattached. The role of the conducting system is to send an electrical impulse to all regions of the heart in a particular order. This electrical impulse, as is seen on an electrocardiogram, represents the signal in each region of the heart as it activates each cell to tell them to start contracting. Sinoatrial Node The sinoatrial node is a specialized region in the superior‐posterior of the right atrium. It is also called the “pacemaker” because this is where each heart beat begins. The cells in this region are more permeable to sodium so as the sodium leaks in, it causes the inside to become more positive (depolarizes), until it reaches threshold and an action potential occurs. This action potential then causes the depolarization of adjacent surrounding cells in a manner that spreads throughout both the right and left atria. This spread of electrical activity through the atria is seen on an electrocardiogram as the P wave. Atrioventricular Node Once the atria have been depolarized, the atrial cells can now contract. The impulse now also arrives at the atrioventricular node located at the inferior septal region of the right atrium. The atroventricular node had two functions. It’s main function under normal circumstances is to relay the electrical impulse from the atria and direct it down to the ventricles via the interventricular septum. In situations where the sinoatrial node may not function properly and does not self‐create a new impulse to start a new beat, the atrioventricular node will self‐generate a beat. This is its second function, it is the ‘backup pacemaker’ of the heart. Like the sinoatrial node, it is also leaky to sodium so it is self‐depolarizing. However, the sodium leak in the atroventricular node is much slower than the sinoatrial node so it takes longer to generate an action potential. Under normal circumstances, the sinoatrial node’s impulse will arrive and stimulate the atrioventricular node before it has a chance to self‐generate one. Because the electrical impulse is in only this one region and relayed to the ventricular septum immediately adjacent, no electrical activity is seen (flat segment) on an electrocardiogram). 44
Bundle of His and Right & Left Bundle Branches Upon leaving the atrioventricular node, the electrical impulse is then transferred to the Bundle of His, located in the superior region of the interventricular septum. The Bundle of His then transfers the electrical impulse to the left and right Bundle Branches in the thicker portion of the interventricular septum. Purkinje Fibers Once the electrical impulse arrives at the apex it then goes back up and all around the free walls of both ventricles in purkinje fibers. These purkinje fibers are what directly activate the cardiomyocytes to contract. The conduction of the electrical impulse from the Bundle of His at the top of the septum down to both Bundle Branches to the apex and back up the sides of the heart, is seen very clearly on an electrocardiogram as the prominent spike, known as the QRS complex. What immediately follows this ventricular activation sequence is ventricular contraction. please label diagram 45
Electrode Placement In order to see the read‐out of the electrical impulses from the heart on a chart or computer screen, recording electrodes must be placed on the patient. These electrodes pick up the electrical changes going on inside the heart as the impulse goes through the atria, down the interventricular septum and out to the free walls. Any depolarizing wave travelling toward a positive electrode will result in a positive deflection on the electrocardiogram. There are two basic electrode placement patterns. Limb leads are placed on the torso surrounding the heart like a triangle. Chest leads are on the chest wall immediately over the heart. If there is an electrical activation across a region of the heart, like the atria, that will be detected by the recording electrodes on the skin and manifest as a wave on an electrocardiogram. The wave can be up (positive) or down (negative), which tells you if the direction of electrical activation is going toward or away from the positive electrode. The size of the wave also tells you how much muscle mass is involved. Atria make small waves, ventricles make big waves. People with ventricular hypertrophy (enlarged muscle mass) have even bigger ECG waves. Limb Leads Four electrodes are placed on either the wrists and ankles or the torso where the arms and legs attach. Three of the electrodes are for recording electrical signals and the fourth acts as a ground or reference electrode. Thus, the recording electrodes form a triangle ‘view’ around the heart. This configuration is known as Einthoven’s triangle. (Einthoven received a Nobel Prize in 1903 for discovering how to record the electrical activity of the heart). Each two‐electrode segments is referred to as a lead. Each lead has a negative electrode and a positive electrode. please label leads and +/‐ electrodes For Lead I, the negative electrode is on the right shoulder and the positive electrode is on the left shoulder. Consider the activation of the sinoatrial node and the depolarization of the atria. The net direction of this depolarization pathway is right to left, which is parallel to Lead I and toward the positive electrode. This results in a positive deflection. For Lead II, the negative electrode is also on the right shoulder and the positive electrode is on the left hip. The net direction of atrial depolarization pathway is right to left, which is consistent with Lead II, however the depolarization pathway is not as well aligned with Lead II as it is with Lead I so the positive deflection from Lead II will be smaller than Lead I. Lead III, is not used as much as I and II. The negative electrode is on the left shoulder and the positive electrode is on the left hip. Although each lead has a different configuration, the resulting electrocardiograms are very similar, they primarily differ in wave amplitude (size). 46
Chest Leads Chest leads are placed on the chest wall directly over the heart. The pattern the electrodes are place is to maximize the coverage of the heart based on the orientation of the heart in the chest. There are six electrodes for the six leads, named V1 through V6., each electrode is over a specific area of the heart. V1 and V2 are over the right atrium and superior interventricular septum, respectively. V3 and V4 are midway down the interventricular septum. V4 is the lower region of the interventricular septum. V5 and V6 are over the lateral and slightly posterior portion of the apex, respectively. Because these leads are so tightly associated with a specific region of the heart, and thus have a different ‘view’ of the heart, the resulting electrocardiogram waveform will not be the same. Consider the depolarization sequence of the interventricular septum from the Bundle of His down through the Bundle Branches to the apex. Remember, any depolarizing impulse that is travelling toward a positive electrode will result in a positive wave, but a depolarizing impulse travelling away from a positive electrode will result in a negative wave or deflection on the recording strip. For example, looking at V5 and V6 at the apex of the heart. The depolarization down the interventricular septum is coming toward V5 and V6 the whole time, so you would correctly guess that the resulting electrocardiogram wave would be positive. In contrast, V1 and V2 are looking at the heart from the atria, above the interventricular septum. The entire interventricular septal depolarization pathway is away from those electrodes. The resulting waveform would be negative. please label V1‐V6 This is a very summarized form of presenting a very complex issue. This is just a very basic way of thinking of heart anatomy and the relationship to the electrode readings on an electrocardiogram. As a general rule, no matter which electrode placement pattern you use (limb leads or chest leads), the one principle stays the same. A depolarizing impulse travelling toward a positive electrode will result in a positive waveform. A depolarizing impulse travelling away from a positive electrode will result in a negative waveform. 47
ELECTROCARDIOGRAM The electrocardiograms that we have all seen before come from limb leads I or II. Each waveform represents a specific electrical event in the heart during the electrical activation or depolarization process. In a single heart beat the waveforms can be broken down into three main waveforms and intervals or segments that are analyzed and noted when evaluating an electrocardiogram. 1. Atrial depolarization, initiated by the sinoatrial node is represented by the first waveform called the P wave. 2. Ventricular depolarization, represented by a complex sequence of waves referred to as the QRS complex, with R as the peak. Q and S may or may not been seen on some tracings but are considered to be the waves or corners on either side of the prominent peak, R. 3. Ventricular repolarization represented as the T wave. (The atria do also repolarize however, the atrial repolarization takes place during the ventricular depolarization. Since the ventricle have a much larger muscle mass, the electrical recording is dominated by the ventricular event, so the atrial event is not observed). P Wave The sinoatrial node depolarization creates an electrical wave across both atria depolarizing the atrial cells. This process is represented on an electrocardiogram as a P wave. The flat line after the P wave is when the impulse is collected in the atrioventricular node and being transferred to the Bundle of His. The impulse does not really travel much so no waveform is detected. The PR interval (it does not really go to R but the corner, Q, below R) is the time from the start of atrial depolarization to the start of ventricular depolarization. QRS Complex The QRS is a number of events bundled together. In general, the depolarizing impulse as it travels through the Bundle of His and to the right and left Bundle Branches is parallel to the recording electrodes in Lead II (shown) so the waveform will be positive. Once the impulse gets to the apex, it then moves out, around, and back up the ventricular free walls. The ST segment is the flat line after the QRS complex during which time ventricular contraction takes place. It is important to understand that the electrical event of depolarization occurs before the mechanical event of contraction. The signal to contract is the QRS complex, the actual contraction has no electrical activity… unless something goes wrong like a heart attack. If the ST segment moves up or down, that could be due to lack of oxygen to a particular area of the heart during contraction. 48
T Wave Ventricular repolarization or electrical recovery is represented as the T wave. Although one would expect it to be the opposite of the QRS complex, it is far from it. The T wave is the sum of many cells throughout the ventricles rebalancing the ions that crossed the membrane during depolarizatoin and there are many differences in the rate of this activity among the ventricular cells. Terminology Sinus rhythm is when all is normal. The heart is ‘paced’ by the sinoatrial node. All waves are present and there is an even spacing between beats. Bradycardia is a heart rate, that is slower than 60 beats per minute. You can see the widely spaced beats indicating a long time between beats. Tachycardia is a heart rate that is faster than 100 beats per minute. You can see that there is very little time between beats. You can see how this may result in limited ventricular filling and therefore low cardiac output and may result in light‐headedness. During exercise, tachycardia is necessary, however there are other adaptations that warrant increased output. Arrhythmias are by definition, an irregular heartbeat. There are many variations in both atrial and ventricular arrhythmia’s and all must be monitored by a cardiologist and most must be treated. 49
CARDIAC ACTION POTENTIAL The ion distribution across a membrane determines the membrane potential. Sodium (Na+), potassium (K+), calcium (Ca++), and chloride (Cl‐) are a few of the ions involved. Cell membranes have channels that allow the ions to cross down its concentration gradient as well as exchange pumps to move ions against their concentration gradient. These are all things that can be affected pharmacologically (with drugs) to alter the depolarization and conduction of action potentials in the heart. Cardiac action potentials are similar to action potentials that occur in neurons, with the exception of the plateau. The rapid depolarization to near +30 mV is similar, but instead of immediately repolarizing to baseline, the cardiac cell maintains the positive membrane potential for almost 200 ms (a whole neuron action potential last for less than 5 ms) before repolarizing. Neuron Voltage (mV) +30 Cardiac cell
0 ‐70 0 Depolarization 100 300 200 Time (ms) 400 500 In both cardiac myocytes and neurons, depolarization is effect of sodium voltage‐gated channels opening, allowing a massive influx of sodium ions in to the cell making the cell more positive. When the cell reaches +30 mV, sodium channels are completely closed and in a locked, refractory position. Plateau In cardiac cells, once the membrane potential reaches +30 mV, calcium voltage‐gated channels open allowing calcium to enter the cell, and potassium voltage‐gated channels open allowing potassium to exit the cell. There is a balance in the positive ions in and the positive ions out, so the membrane potential remains constant until the calcium channels close and other potassium channels open. This prolongation of the action potential prevents cardiac muscle from having another contraction too soon, before filling can take place. We need our heart muscle to contract and then relax. Repolarization Repolarization or return to resting membrane potential is achieved by closing the calcium channels to stop the influx of calcium and opening of potassium channels (there are many different potassium channels). As potassium exit the cell, the membrane potential becomes more negative until it reaches around ‐90 mV (a little more negative than a neuron). It is at this point the exchange mechanisms and pumps for sodium, potassium, and calcium re‐establish the concentration gradients so another action potential can occur for a subsequent beat. 50
Role of Ions Sodium’s (Na+) primary role is in the depolarization of the pacemaker cells. The leaky‐er the cell is, the sooner the cell can develop an action potential. A drug that is a sodium‐channel blocker will cause the heart rate to slow down because it makes it harder for sodium to leak into the cell and start a new action potential (great to slow down tachycardia). Calcium (Ca++) not only is the reason the action potential is maintained for so long, but it contributes to the contractile activity of the cardiac cell. Drugs that are calcium channel agonists (promote opening) will increase the force of contraction. In contrast, calcium channel blockers will reduce the force of contraction and can be used to treat high blood pressure. Potassium(K+)is critical in getting the membrane potential back to negative values by letting the positive ion, potassium out of the cell. Drugs that are potassium channel blockers will make it harder for potassium to leave the cell so it will prolong the repolarization phase making the cell take longer to achieve resting membrane potential. This type of drug is used to prevent atrial arrhythmias and to slow down the heart rate. 51
CARDIAC CYCLE The sequence of events that occurs in a single heart beat is known as the cardiac cycle. There are two main stages for the atria and ventricles, diastole and systole. Diastole is when the heart muscle is resting and the chambers are filling with blood. Systole is when the heart muscle is contracting and generating force in order to push the blood out. The representation of simultaneous pressure and volume measurements was popularized by Dr. Carl Wiggers, MD and is now referred to as the Wiggers diagram. Ventricular Filling The cardiac cycle begins with the blood returning to the atria and filling the ventricles by going through the open atrioventricular valves. The ventricles are passively expanding so pressure is near 0. The heartbeat has not yet been initiated so there isn't any electrical activity. Pressure in the aorta is falling since the heart is not sending any blood out yet. Atrial Contraction After the P wave initiates atrial contraction, blood is pumped from the atria to the ventricles, giving the ventricles one last surge of blood, topping them off. The P wave occurs right before the actual contraction, which is observed by a slight rise in ventricular pressure as it 'feels' the surge of blood. Ventricular volume also surges upward to reflect the sudden, rapid, small increase in filling. Pressure in the aorta continues to decline since the heart is still not sending any blood out yet. Isovoloumic Contraction Following atrial contraction, the QRS complex activates the ventricles initiating ventricular contraction. Ventricles contract increasing pressure, shutting the atricventricular valve, but not the aortic valve so blood is not going anywhere. The left ventricle hasn't developed enough pressure to push open the aortic valve to eject the blood. This is what isovolumic means (iso = same and volumic = volume). Ventricular pressure shows a rapid rise due to the great increase in pressure as the ventricles are squeezing inward. Since the pressure in the ventricle has not yet reached the same as in the aorta just outside the aortic valve, the aortic pressure continues to decline since the heart is still not sending any blood out yet. Ventricular Ejection Once the left ventricle has squeezed hard enough to generate the amount of pressure to equal the diastolic blood pressure (80 mm Hg for a person with a blood pressure of 120/80), then the aortic valve can open. The ventricle continues to squeeze, but now the blood can finally exit the heart and enter the aorta. You can imagine how much harder a person’s heart has to squeeze just to eject blood in people with high blood pressure. Once the aortic valve opens, the aortic and left ventricular pressure increase together as the heart is still squeezing and generating force. At the same time, there is a rapid decline in left ventricular volume because the blood is leaving the heart and going out to the body. There should be no electrical activity at this time. 52
Ventricular Relaxation When the ventricle begins to relax, as seen by the T wave (the only time the electrical event occurs simultaneously with the muscular activity), pressure start to drop. The drop in pressure is associated with a tapering off of volume ejection. The drop in pressure in the aorta causes the aortic valve to close as the blood in the immediate vicinity of the valve tries to go backward into the ventricle due to the dropping pressure there. The blood catches in the flaps of the semilunar valve and seals it shut, the blood actually bounces off the valve and surges forward again and is reflected as a jog in the aortic pressure known as the dicrotic notch. Isovolumic Relaxation Once the semilunar valves close, blood can no longer leave the heart. The pressures within the ventricle are still high, even though they are declining. Therefore, no new blood can enter, so volume remains constant. This is the isovolumic relaxation phase, where blood does not exit or enter the ventricle as the myocardium relaxes. Ventricular Filling Once the ventricular pressure drops all the way back to zero, the pressure in the ventricle becomes lower than in the atria, which have been holding all the incoming blood. When the ventricular pressure drops below atrial pressure, the atrioventricular valves open, and blood comes surging into the heart. This is seen as a rapid increase in ventricular volume which is known as ventricular filling. The pressure is low during this time as the heart just passively expands like a water balloon. The aortic pressure is independent of what is going on in the ventricles since the aortic valve is closed, so the aortic pressure just continues its steady decline as blood goes out to the body. 53
CARDIAC OUTPUT The cardiac volumes are all centered around the main pump, the ventricle. At the end of the filling phase during diastole, when the heart is at rest, the ventricles are the most full. This is the end‐diastolic volume (EDV). After the ventricle has gone through the systolic phase of contraction and ejecting blood out to the aorta, what is left over in the ventricle is called the end‐systolic volume (ESV). The amount of blood that actually left the heart and entered the aorta is the stroke volume (SV). This is calculated by subtracting the end‐systolic volume or what was left over from the end‐diastolic volume or what the heart started with when it was a its fullest. An ultrasound of the heart can measure the dimension of the ventricle and give a value for the end‐diastolic volume and end‐systolic volume. The ejection fraction is a term often used to describe the level of function of a person’s heart. The ejection fraction is just stroke volume expressed as a percent. Write the values for: EDV: ______________mL ESV: _______________mL SV: ________________mL Cardiac output is how much blood can the heart pump out in one minute. The amount of blood ejected in a single beat is stroke volume. The number of times the heart beats in a minute is the heart rate. Multiply these two numbers together and you have the cardiac output. Cardiac Output (mL/min) = Stroke Volume
(mL/beat) X
Heart Rate (beat/min) During exercise, cardiac output increases to accommodate the increased oxygen demand by the working muscles. At rest, a normal cardiac output is around 5000 mL/min or 5 L/min. During exercise, cardiac output can reach 22 L/min in an untrained individual or 35 L/min in a trained athlete. One big difference in cardiac output is the ventricle size. Ventricular chamber size is greater In trained athletes so they have a larger stroke volume for every beat, so their heart does not have to pump as many times in a minute to get the same cardiac output out. Even at maximal exercise, the heart rates are the same for trained and untrained athletes, but they eject different amounts of volume. Therefore, the trained athlete has a greater output of blood per minute, delivering more oxygen and thus, increasing exercise capacity. 54
Factors Affecting Cardiac Output Some of the factors affecting cardiac output are the things that affect heart rate and stroke volume. The heart rate can increase with sympathetic stimulation or decrease with parasympathetic stimulation. Many different hormones have cardiac effects. The most common are the sympathetic hormones from the adrenal medulla, epinephrine and norepinephrine. Both increase heart rate. The thyroid hormone thyroxine or T4 can also increase heart rate. Increased venous return causing expansion of the atria can increase heart rate. Stroke volume is affected by how much the ventricle fills or preload. The greater the filling the more the myocardium stretches, which increases the force of contraction from the myocardium. Afterload is one of the biggest factors affecting stroke volume. The afterload is the pressure the heart has to pump against which is the blood pressure in the aorta. Cardiac contractility or the force of contraction by the myocardium affects stroke volume. The greater the force generated by the heart the more volume can be ejected from the heart. Frank‐Starling Law The Frank‐Starling Law of the heart is the reason behind why the greater the filling of the heart the greater force generated by the heart. When more blood fills the heart, the muscle stretches more. This stretch actually affects troponin inside the ventricular muscle cells causing a greater shift in tropomyosin, exposing more active sites on actin resulting in more cross‐bridge formation. The more cross bridges you can form, the more force the muscle can make. Therefore, instead of relying on the nervous system or hormones to increase the contractile force of the heart, just an increase in returning blood volume or preload to stretch the muscle cells will help the heart to eject more blood and contract more forcefully. This is one of the main mechanisms people with a heart transplant can adjust their cardiac output during the early phase of exercise before any augmenting hormones such as epinephrine or norepinephrine begin to circulate. 55
HEART SUMMARY P ART O NE : E XTERNAL A NATOMY 1. Describe the serous membrane surrounding the heart. 
The serous membrane is folded over on itself to make of two layers. The visceral pericardium is fused with the epicardium, the outermost layer of the heart wall, and the parietal pericardium that looks like a sac surrounding the heart. 2. Describe the superficial features of the heart. 
When viewing the hearts exterior you will see the following features: o Great vessels on top: pulmonary artery and aorta o Superior and inferior vena cava entering the right atrium and the pulmonary veins entering the left atrium o The right atrium and auricle and left atrium and auricle o Right and left ventricles covered with coronary arteries and veins embedded within protective fat pads. 3. What are the muscular layers of the heart? 
Epicardium: outermost layer 
Myocardium: thickest layer where contractile cardiac muscle is found  Endocardium: innermost layer that is touching the blood within the ventricles 4. Name the largest coronary arteries and describe the specific regions of the heart each of those arteries serve. 
Left main coronary artery is just a centimeter long before it splits into: o Left anterior descending artery that supplies the interventricular septum and the left ventricle with blood o Left circumflex artery that supplies the lateral and posterior portions of the left ventricle  Right main coronary artery that serves the right side of the heart 5. Name the main veins on the heart and describe how the deoxygenated blood gets to the right ventricle. 
Great cardiac vein is found wrapping around the posterior surface receiving blood from the left side of the heart 
Anterior interventricular vein found along the anterior middle surface of the heart drains blood from the interventricular septum 
Middle and posterior cardiac vein drains blood from the left side of the heart 
Middle cardiac vein drains blood from the lateral surface 
Anterior cardiac vein drains blood from the right side 
All the veins drain into the coronary sinus which sends the blood directly into the right atrium. 56
P ART T WO : I NTERNAL A NATOMY 1. Name the chambers of the heart and indicate if the blood is oxygenated or deoxygenated. 
Right atrium: deoxygenated 
Right ventricle: deoxygenated 
Left atrium: oxygenated  Left ventricle: oxygenated 2. What is the role of the right ventricle?  To eject blood to the pulmonary circulation (lungs) 3. What is the role of the left ventricle?  To eject blood to the systemic circulation (body) 4. What type of valve is the tricuspid valve? What is the function of that valve? What are the important features of that valve? 
Atrioventricular valve. 
Prevents blood from going backward from the right ventricle to the right atrium 
Three thin, strong flaps connected to chordate tendinae attached to papillary muscles within the right atrium 5. What is the difference between an atrioventricular valve and a semilunar valve? Give an example of each. 
Atrioventricular valves (mitral and tricuspid) have flaps and chordate tendinae and are found between the atria and ventricles. 
Semilunar valves (pulmonary and aorta) each have three flaps attached to the base of the vessel walls. 6. Describe the pathway of blood flow for a drop of blood going from the right ventricle to the left ventricle. 
Blood leaving the right ventricle goes through the pulmonary semilunar valve to the pulmonary circulation. 
Blood then leaves the pulmonary circulation through the pulmonary veins, entering the left atrium, crossing the mitral valve and entering the left ventricle. 7. What valves are open or closed during ventricular ejection? 
During ejection of blood out of the heart, both the atrioventricular valves (tricuspid and mitral) are closed to prevent backflow into the atria. 
Both the pulmonary and aortic semilunar valves are open to allow blood to leave the heart and enter the pulmonary and systemic circulations. 8. At what point during the contraction cycle of the heart does coronary blood flow cease or stop momentarily? 
Coronary blood flow (blood supply to the heart muscle) stops when the heart is contracting during ejection of blood out of the heart. 9. What causes the first heart sound? 57

The first heart sound occurs when the ventricles begin to contract causing the atrioventricular valves to slam shut. 10. What is the heart doing before the first heart sound? 
Before the pressure development in the ventricles that caused the atrioventricular valves to slam shut, the atrioventricular valves were open allowing blood to flow into the ventricles. P ART T HREE : E LECTRICAL C ONDUCTION 1. List the features of the electrical conducting system in the heart. For each feature, indicate where it is located. 
Sinoatrial node in the right atrium 
Atrioventricular node found at the base of the right atrium near the septum 
Bundle of His found in the superior region of the interventricular septum 
Right bundle branch found on the right side of the interventricular septum 
Left bundle branch found on the left side of the interventricular septum  Purkinje fibers found throughout the fee walls of the ventricles 2. Name the waves on an electrocardiogram. For each wave you name, please indicate what happened in the heart (or what the heart did) to cause the wave. 
P wave: Sinoatrial node initiated depolarization of atria 
QRS complex: depolarization of the ventricles (Bundle of His, bundle branches, and purkinje fibers)  T wave: repolarization of the ventricles 3. Where are the electrodes located when one is viewing a Lead I electrocardiogram? What electrical pathway or activation sequence in the heart is Lead I parallel to? 
There is a negative electrode on the right shoulder (or right wrist) and a positive electrode on the left shoulder (or left wrist). 
This is parallel to the activation pathway of the atria from the sinoatrial node across the right atrium and left atrium 4. What is happening in the heart during the P‐R interval? 
This is after atrial depolarization so the atria are contracting and pushing blood into the ventricles. 
There is also an electrical delay going on in the atrioventricular node before the impulse travels to the Bundle of His and down the interventricular septum. 5. Name the electrical wave or segment on an electrocardiogram that occurs at the same time the ventricles are contracting and ejecting blood?  S‐T segment 6. What electrocardiogram wave represents ventricular repolarization? 
T wave 58
7. What electrical activity in the heart creates a positive wave on an electrocardiogram? Use Lead I for the Lead in your explanation. 
Depolarization from the right atrium across to the left atrium (P wave) o The direction of depolarization is away from the negative electrode on the right side and toward the positive electrode on the left side 
Depolarization down the interventricular septum o The direction may be downward, but since the hearts apex is tipped leftward the vector of depolarization is still away from the negative electrode on the right shoulder and toward the positive electrode on the left side. 
Repolarization of the ventricles P ART F OUR : C ARDIAC C YCLE & C ARDIAC O UTPUT 1. During ventricular systole, what are the atria doing?  Filling with blood 2. What is end‐diastolic volume? When does the heart achieve this volume?  The volume of blood in the ventricles at the end of filling (~130 mL) 3. What is end‐systolic volume? What is a normal value for end‐systolic volume?  The volume of blood at the end of ejection (~ 50 mL) 4. Statistics for John Adams: heart rate 70 beats per minuet, blood pressure 150/ 120 mm Hg, end‐
systolic volume 130 mL, end‐diastolic volume 60 mL, ejection fraction 46%. What is his cardiac output? Show the math you did to calculate your answer. 
Cardiac Output = Stroke volume X Heart Rate o Stroke volume = End diastolic volume (130 mL) ‐ End systolic volume (60 mL) = 70 mL per beat o Heart rate = 70 beats per minute  4900 mL/min = 70 mL/beat X 70 beats/ minute 5. Name 3 factors that can augment cardiac output. How do those factors increase cardiac output? 
Autonomic nervous system o Parasympathetic will decrease heart rate, decreasing cardiac output o Sympathetic will increase heart rate and contractility increasing cardiac output 
End‐diastolic volume & End‐systolic volume o The more filling the heart gets, the more blood it can eject o The more the heart ejects, the less the end‐systolic volume is 
Venous return o Increased venous return increases ventricular filling (and end‐diastolic volume) which will increase the contraction of the heart so the heart ejects he blood more forcefully. 59
o

This seems the same as more blood in so more blood out, but the stretch of the ventricles with the extra blood in actually causes the heart muscle to contract harder, ejecting a greater percentage of blood out (ejection fraction). Cardiac contractility o Any hormone or Frank‐Starling law action that increases the contraction of cardiac muscle will increase cardiac output o Any damage to the heart will decrease contractility so cardiac output will be diminished. 
Afterload o High blood pressure makes it harder for the heart to eject blood out. So high blood pressure will decrease cardiac output, unless the heart can compensate and increase the muscle mass (cardiac hypertrophy). o Low blood pressure allows a greater percentage of blood to be ejected out of the heart and increase cardiac output. 6. What is the effect of increased venous return on cardiac myocytes? 
The increased venous return stretches the ventricles like a water balloon. The stretched cardiac cells are affected internally by allowing troponin to move more tropomyosin bands, exposing more crossbridge binding sites so that more force can be developed. This all occurs without increasing intracellular calcium levels. So the same calcium release from the sarcoplasmic reticulum will cause more active sites to be exposed and more crossbridges to form, developing more force an d ejecting more blood. 60
HEART STUDY ACTIVITIES EXERCISE 1: CORONARY ARTERY IDENTIFICATION The shaded regions indicate some of the areas served by three coronary arteries (right ventricle, left ventricle, interventricular septum, lateral left ventricle, posterior left ventricle). For each colored region, name the artery that delivers blood to that area. Exercise 2: Electrical Conduction Pathway For part of the heart listed, name the electrical region in the heart that is found there and the electrocardiogram waveform associated with activity in that electrical region. Cardiac Region Right Atrium: superior, posterior Right atrium: superior, medial Interventricular septum: superior portion Interventricular septum: medial and lower Ventricular free walls Electrical node or pathway 61
EXERCISE 3: ELECTROCARDIOGRAM On the graph below, draw an electrocardiogram tracing for a single heart beat. Using the items listed in the table below, electrocardiogram tracing you drew. On the table, indicate what is going on in the heart during the time of each item listed. Electrocardiogram Waveform Electrocardiogram Table Wave/Interval/Segment
P wave P‐R interval QRS complex S‐T segment T wave Action Please define the following terms: Sinus rhythm _________________________________________________________________________ Bradycardia ___________________________________________________________________________ Tachycardia __________________________________________________________________________ Arrhythmia ___________________________________________________________________________ 62
EXERCISE 3: CARDIAC CYCLE Please complete the cardiac cycle diagram below. Label the pressure axis and the volume axis using the patient data provided . Use the legend to indicate the colors for the lines representing each wave and circles for each valve event. Please indicate the region on the pressure and volume graphs for isovolumic contraction and isovolumic relaxation. Note that the diagram represents two cardiac cycles. Patient Data Heart Rate 72 beats/min Stroke Volume ________ ‐ ________ = _________ mL End‐Diastolic Volume 135 mL End‐Systolic Volume 65 mL Blood Pressure 130/85 Cardiac Output ________ x ________ = _________ mL/min ECG Pressure (mm Hg) Volume (mL) Time (ms)
Legend: Electrocardiogram Aortic pressure LV volume Mitral valve CLOSE AV
Aortic valve CLOSE SL
Mitral valve OPEN AV
Aortic valve OPEN 63
SL
EXERCISE 4: CARDIAC ANATOMY Please label and color the regions indicated. anterior posterior Aorta Pulmonary Artery Right Atrium Left Atrium Right Ventricle Left Ventricle Right Coronary Artery Right Marginal Artery Left Anterior Descending Artery Pulmonary Veins Superior Vena Cava Inferior Vena Cava Right Atrioventricular (Tricuspid) Valve
Left Atrioventricular (Mitral) Valve Pulmonary Semilunar Valve Chordae Tendineae Papillary Muscles Parietal Pericardium Visceral Pericardium interior 64
HEART QUESTIONS THESE QUESTIONS ARE INTENDED TO GUIDE YOU TOWARD A DETAIL AND EMPHASIS IN STUDYING BY TRYING TO HELP CONNECT SEVERAL CONCEPTS TOGETHER. IT IS IMPORTANT TO FIND THE RIGHT ANSWER(S), AS WELL AS KNOW WHY THE WRONG ANSWERS ARE INCORRECT. 1.
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What chamber is initiated to contract by the QRS complex and contains oxygenated blood? a. Right atrium b. Left atrium c. Right ventricle d. Left ventricle Which way does the apex of the heart “point”? a. Superior and laterally to the left b. Laterally to the right c. Inferior and to the left d. Superior The only deoxygenated artery in the body is the _________. a. Aorta b. Left coronary artery c. Right coronary artery d. Pulmonary artery What is the purpose of the coronary arteries? a. Deliver blood to the body during ventricular systole b. Deliver blood to the lungs during ventricular diastole c. Deliver blood to the heart muscle during ventricular diastole d. Deliver blood to the heart muscle during ventricular systole Where does the coronary sinus drain into? a. Superior vena cava b. Left atrium c. Right atrium d. Great cardiac vein e. Aorta 65
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Where are musculi pectinati located? a. On atrioventricular valves b. On semilunar valves c. Inside atria d. Inside ventricles Where does deoxygenated blood from the body enter the heart? a. Coronary sinus b. Right ventricle c. Pulmonary artery d. Right atrium e. Left atrium Deoxygenated blood is in all of the following locations, except… a. Passing through the right atrioventricular (tricuspid) valve b. Coronary sinus c. Pulmonary artery d. Around musculi pectinati in left atrium e. Inferior vena cava f. Passing through the pulmonary semilunar valve Which valve(s) are attached with chordae tendineae? a. Tricuspid and pulmonary semilunar b. Tricuspid and aorta c. Pulmonary semilunar and aorta d. Mitral and tricuspid e. Mitral and aorta f. Mitral and pulmonary semilunar The left ventricle has every feature except _________. a. Chordae tendineae b. Thick free wall c. Papillary muscles d. Pulmonary semilunar valve e. Trabeculae carneae 66
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The papillary muscles a. Are ridge‐like muscles that line the atria and assist with contracting b. Help prevent blood from moving from the ventricles into the atria c. Take up slack on chordae tendineae, holding atrioventricular valves closed d. Are irregular ridges of muscle lining the ventricles e. Both B and C are correct f. None of the above Diastolic blood pressure is the pressure that __________. a. the ventricle reaches to open the aortic valve b. is the peak pressure generated by the ventricle c. helps to fill the ventricles with blood d. opens the atrioventricular valves e. Both A and B are correct f. Both C and D are correct The aorta __________. a. comes contains blood directly from the lungs b. carries deoxygenated blood to the pulmonary artery c. feeds oxygenated blood to the coronary arteries d. receives blood through the aortic tricuspid valve Oxygenated blood travels __________. a. through aorta to lungs, via pulmonary veins to left atrium, through left bicuspid valve to left ventricle then out to body b. to heart through pulmonary veins, through left atrium, through left semilunar valve into the left ventricle then out to the body via aorta c. from lungs to heart via pulmonary arteries, through the left atrioventricular valve into the left atrium, to the left ventricle and out to the body via aorta d. from lungs to heart via pulmonary veins, into the left atrium, through the left mitral valve, into the left ventricle and out to body through aorta The second heart sound is caused by __________. a. ventricular contraction b. atrioventricular valve opening c. semilunar valve closure d. ventricular ejection e. atrioventricular valve closure 67
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The P wave is followed by ________. a. atrial depolarization b. atrial contraction c. ventricular depolarization d. ventricular contraction e. ventricular relaxation Semilunar valves open up to release ventricular blood_______. a. during repolarization of ventricles. b. when the Bundle of His depolarizes. c. during ventricular diastole. d. at the peak of the R wave. e. after atrioventricular valves open. f. at the end of isovolumic contraction. The correct sequence of cardiac depolarization is __________. a. Right Bundle Branch & left Bundle Branch, Bundle of His, Sinoatrial node, Atrioventricular node, purkinje fibers b. Atrioventricular node, Sinoatrial node, right Bundle Branch & left Bundle Branch, Bundle of His, purkinje fibers c. Sinoatrial node, Atrioventricular node, right Bundle Branch & left Bundle Branch, Bundle of his, purkinje fibers d. Sinoatrial node, Atrioventricular node, Bundle of His, right Bundle Branch & left Bundle Branch, purkinje fibers e. sinoatrial node, atrioventricular node, Bundle of His, purkinje fibers, right Bundle Branch & left Bundle Branch Which of the following is NOT true of the sinoatrial node? a. It normally initiates each new heartbeat b. It is more permeable to sodium than the atrioventricular node c. It can reach threshold on it’s own (doesn’t require innervation) d. It is located in the superior‐posterior region of the right atrium e. It’s depolarization follows atrial contraction 68
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Surface electrodes on the body detect __________. a. Electrical activity within the heart b. Direction of the depolarizing wave c. Direction of depolarizing wave according to electrode placement d. Force of contraction by the ventricles e. All of the above f. All of the above except C and D g. All of the above except D For Einthoven’s triangle Lead II (right shoulder to left hip), which is FALSE? a. When the depolarization impulse travels down the interventricular septum, it goes toward a positive electrode, making a positive ECG wave. b. When the purkinje fibers depolarize, the vector of depolarization moves away from a positive electrode, making a negative ECG wave. c. During atrial systole there is no net vector of depolarization visible, so there is not ECG wave (it is flat). d. During ventricular systole there is no net vector of depolarization visible, there is not ECG wave (it is flat). e. During ventricular depolarization there is no electrical activity so there is a negative ECG wave. Which of the following is responsible initiating depolarization of the cardiac (and neuron) action potential? a. Calcium influx b. Calcium efflux c. Sodium influx d. Sodium efflux e. Potassium influx f. Potassium efflux Which of the following is responsible for prolonging the state of depolarization in cardiac muscle, a.k.a. maintaining the plateau phase? a. Calcium influx b. Calcium efflux c. Sodium influx d. Sodium efflux e. Potassium influx f. Potassium efflux 69
Which of the following is responsible for allowing cardiac muscle cells (and neurons) to return to their resting membrane potential (repolarization)? a. Calcium influx b. Calcium efflux c. Sodium influx d. Sodium efflux e. Potassium influx f. Potassium efflux 25.
List the proper sequence the following cardiac events take place: i.
Atrial contraction ii.
Ventricles depolarize iii.
Isovolumic contraction iv.
Ventricular pressure exceeds aortic pressure v.
Semilunar valve opens vi.
T wave vii.
P wave a. i, vii, iii, vi, iv, ii, v b. vii, i, ii, iii, iv, v, vi c. vii, ii, i, iv, iii, v, vi d. vi, v, iii, iv, vii, ii, i 26. More crossbridges that form, the harder the heart will contract. a. True b. False 27. Heart rate affects cardiac output. a. True b. False 28. A stronger systole is usually associated with small end diastolic volume. a. True b. False 24.
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HEART TERMS EXTERNAL ANATOMY ELECTROPHYSIOLOGY Apex Pulmonary artery Aorta Superior vena cava Inferior vena cava Right atrium Left atrium Right ventricle Left ventricle Parietal pericardium Visceral Pericardium Epicardium Myocardium Endocardium Left main artery Left anterior descending artery Left circumflex artery Right coronary artery Right marginal arteries Posterior interventricular artery Coronary sinus Sinoatrial node Atrioventricular node Bundle of His Right bundle branch Left bundle branch Purkinje fibers Pacemaker P wave QRS complex T wave ST interval Limb leads (I‐III) Chest leads (V1 ‐ V6) Sinus rhythm Bradycardia Tachycardia Arrhythmia Ions: Sodium, Potassium, Calcium, Chloride Resting membrane potential Depolarization Repolarization Plateau INTERNAL ANATOMY CARDIAC CYCLE Right atrium Left atrium Fossa ovalis Musculi pectinati Atrioventricular valves Tricuspid valve Bicuspid valve Mitral valve Chordae tentineae Papillary muscles Right ventricle Left ventricle Trabeculae carneae Pulmonary semilunar valves Aortic semilunar valve Systole Diastole Ventricular filling Ventricular ejection Ventricular relaxation Isovoumic contraction Isovolumic relaxation End‐diastolic volume End‐systolic volume Stroke volume Ejection fraction Cardiac output Preload Afterload Contractility Frank‐Starling's Law 71