Exam 3 Pages 16-35 Pathology PDF

7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 1/19/2023 Hunger, Appetite, and Control Mechanisms of Food Intake The sensation...

7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 1/19/2023 Hunger, Appetite, and Control Mechanisms of Food Intake The sensation of hunger is associated with several sensory perceptions, such as the rhythmic contractions of the stomach and that “empty feeling” in the stomach that stimulates a person to seek food. A person’s appetite is the desire for a particular type of food. It is useful in helping the person determine the type of food that is eaten. Satiety is the feeling of fullness or decreased desire for food. Two centers in the brain interact with various hormones and neurotransmitters to help control food intake and energy output. The arcuate nucleus of the hypothalamus has been identified as the center for hunger and satiety. Other centers in the brainstem also contribute to the mechanisms.10 These centers receive neural input from the gastrointestinal tract that provides information about stomach filling, chemical signals from nutrients (glucose, amino acids, and fatty acids) in the blood, and input from the cerebral cortex regarding the smell, sight, and taste of the food. Centers in the hypothalamus also control the secretion of several hormones (e.g., thyroid and adrenocortical hormones) that regulate energy balance and metabolism. The control of food intake is subject to short-term regulation, which is concerned with the amount of food that is consumed at a meal or snack, and intermediate- and long-term regulation, which is concerned with the maintenance of energy stores over time.11 Neuro-hormones are responsible for the short-term regulation of food intake either by increasing feeding considered to be orexigenic or decreasing feeding classified as anorexigenic.11 Figure 39.2 lists several of these neural messengers and the overall effects they promote. Over 30 gastrointestinal hormone genes have been identified that play a role in regulating hunger and satiety.12 Research is providing additional insights into the complex system; however, much is still unknown.12,13 Figure 39.2 The balance of chemical mediators impacting weight gain and loss. ACRP, adipocyte complement–related protein; GLP, glucagon-like peptide; NPY, neuropeptide Y; PPAR, peroxisome proliferator–activated receptor. (From Strayer D., Rubin R. (Ed.) (2015). Rubin’s pathology: Clinicopathologic foundations of medicine (7th ed., Figure 13-1, p. 517). Philadelphia, PA: Lippincott Williams & Wilkins. Three main short-term messengers that promote orexigenic effects include ghrelin, produced mainly in the stomach, and neuropeptide Y (NPY) and agouti-related protein (AGRP), both produced in the hypothalamus. Many of the other gut hormones have anorexigenic effects by signaling satiety to the neural centers. All of these messengers send messages of satiety that ultimately help decrease food intake.10 The intermediate- and long-term regulation of food intake is determined by the amount of nutrients that are in the blood and in storage sites. It has long been known that a decrease in blood glucose causes hunger. In contrast, an increase in breakdown products of lipids such as ketoacids produces a decrease in appetite. A ketogenic weight-loss diet (e.g., the Atkins diet) relies partly on the appetite-suppressant effects of ketones in the blood. Adipocytes release leptin in proportion to the amount of fat stores. The stimulation of leptin receptors in the hypothalamus produces a decrease in appetite and food intake as well as an increase in PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created metabolic rate and energy consumption. It also produces a decrease by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's in insulin release from the beta cells, which decreases energy storage prior permission. Violators will be prosecuted. in fat cells.14 IN SUMMARY The body requires more than 40 nutrients about:blank 220/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology on a daily basis. Nutritional status reflects the continued daily intake of nutrients over time and the deposition and use of these nutrients in the body. The DRIs classify the amounts of essential nutrients considered to be adequate to meet the known nutritional needs of healthy people. The DRIs have 22 age and sex classifications and include recommendations for calories, proteins, fats, carbohydrates, vitamins, and minerals. Hunger and satiety are controlled by a complex group of neurohormones, many of which are produced in the gastrointestinal tract. These messengers function to either stimulate hunger or signal satiety to control both short- and long-term effects. Although much information has been revealed through research in recent years, there is still much to be learned in order to effectively manage the complex process more effectively. OVERWEIGHT AND OBESITY After completing this section of the chapter, the learner will be able to meet the following objectives: Explain the use of body mass index (BMI) in evaluating body weight. Define and discuss the causes and types of obesity and health risks associated with obesity. Discuss the treatment of obesity in terms of diet, behavior modification, exercise, social support, pharmacotherapy, and surgical methods. Obesity is defined as having excess body fat accumulation with multiple organ-specific pathologic consequences. Overweight and obesity have become global health problems. In 2016, 1.9 billion people were classified as overweight; 650 million were further classified as obese. In the United States, more than 65% of adults are currently either overweight or obese, and more than 36.5% of the population is obese, with obesity having an even higher prevalence in minority groups such as non-Hispanic Blacks and those of Hispanic ethnicity.15 The prevalence of overweight and obesity is even more alarming in children and adolescents. Approximately 17% of children between 2 and 19 years of age are obese—a percentage that has tripled since 1980.16 Exam three content. Energy Storage. Adipose tissue as an endocrine organ and control of appetite. Important 8/25/2022 Figure 39.7 Clinical manifestations of kwashiorkor. Important 8/16/2022 Diagnosis Malnutrition and Starvation. Diagnostic labs. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 221/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 1/19/2023 No single diagnostic measure is sufficiently accurate to serve as a reliable test for malnutrition. Techniques of nutritional assessment include evaluation of dietary intake, anthropometric measurements, nutrition-focused physical examination, and laboratory tests.43 Evaluation of body composition can be assessed with weight, edema, muscle wasting, and subcutaneous fat loss. Serum albumin and prealbumin are used in the diagnosis of protein–calorie malnutrition. Albumin, which has historically been used as a determinant of nutrition status, has a relatively large body pool and a half-life of 20 days and is less sensitive to changes in nutrition than prealbumin, which has a shorter half-life and a relatively small body pool.43 Treatment The treatment of severe protein–energy malnutrition involves the use of measures to correct fluid and electrolyte abnormalities and replenish proteins, calories, and micronutrients. Treatment is started with modest quantities of proteins and calories based on the person’s actual weight. Concurrent administration of vitamins and minerals is needed. Either the enteral or parenteral route can be used. The treatment should be undertaken slowly to avoid complications. The administration of water and sodium with carbohydrates can overload a heart that has been weakened by malnutrition and result in heart failure. Enteral feedings can result in malabsorptive symptoms because of abnormalities in the gastrointestinal tract. Refeeding edema is benign-dependent edema that results from renal sodium reabsorption and poor skin and blood vessel integrity. It is treated by elevation of the dependent area and modest sodium restrictions. Diuretics are ineffective and may aggravate electrolyte deficiencies. Exam three content Important 8/16/2022 Treatment Important 1/19/2023 TABLE 40.1 Major Action and Source of Selected Hormones Exam three content. Chapter 41. Disorders of Endocrine Control of Growth and Metabolism. Page 1175, Table 40.1 and/or Course Point Activity-Picmonic: Adrenal Gland (advanced). Describe the hormones produced by the adrenal gland. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 222/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 Hypothalamic–Pituitary Regulation The hypothalamus and pituitary gland form a functional unit that exerts control over the activities of several endocrine glands, and thus a wide range of physiologic functions. The hypothalamus is located centrally in the brain and serves as the coordinating center of the brain for endocrine, behavioral, and autonomic nervous system function. It is at the level of the hypothalamus that emotion, pain, body temperature, and other neural inputs are communicated to the endocrine system.3 The pituitary gland is connected to the floor of the hypothalamus by the pituitary stalk, with the main structural portion of the pituitary gland encased in a bony structure called the sella turcica. The opening to the sella turcica is bridged over by the diaphragma sellae, which protects the pituitary gland from the transmission of the pressures from the cerebrospinal fluid.6 The pituitary gland is also called the “hypophysis.” The pituitary consists of two structurally different sections (Fig. 40.2): Figure 40.2 The hypothalamus and the anterior and posterior pituitary. The hypothalamic releasing or inhibiting hormones are transported to the anterior pituitary through the portal vessels. ADH and oxytocin are produced by nerve cells in the supraoptic and paraventricular nuclei of the hypothalamus and then transported through the nerve axon to the posterior pituitary, where they are released into the circulation. a. The anterior pituitary, also called the adenohypophysis because of its glandular structure. The hypothalamus and anterior pituitary are connected by blood flow through the hypophysial portal venous system, which begins in the hypothalamus and drains into the anterior pituitary gland. b. The posterior pituitary, also called the neurohypophysis. The hypothalamus and posterior pituitary are connected through nerve axons from neurons that originate in the hypothalamus and connect the supraoptic and paraventricular nuclei of the hypothalamus with the posterior pituitary gland. Hypothalamic Hormones. The hypothalamus produces hormones that act upon the anterior pituitary to regulate the synthesis and release of anterior pituitary hormones. These hypothalamic hormones are called releasing or inhibiting hormones, based on the response sent to the anterior pituitary. Releasing hormones (RHs) signal for the anterior pituitary to increase the synthesis and release of a particular hormone, whereas inhibiting hormones have the reverse effect—decreased hormonal release by the anterior pituitary. These releasing and inhibiting hormones travel to the anterior pituitary through a localized portal venous system2,3 (Fig. 40.2). The hypothalamic hormones that regulate the secretion of anterior pituitary hormones include GH-releasing hormone (GHRH), somatostatin, dopamine, TRH, corticotropin-releasing hormone (CRH), and gonadotropin-releasing hormone (GnRH).2,3 The hypothalamus also sends regulatory signals to the posterior pituitary; however, the route through which the message is conducted is through nerve tracts instead of through release of hormones into the blood. The posterior pituitary is called the neurohypophysis because it contains a series of neurons whose cell bodies are located in the hypothalamus and axons extend down into the posterior pituitary. The posterior pituitary can essentially be thought of as an extension of the hypothalamus. The posterior pituitary hormones, ADH and oxytocin, are synthesized PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created in the cell bodies of neurons in the hypothalamus that have axons by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's that travel to the posterior pituitary.2,3 The activity of the prior permission. Violators will be prosecuted. hypothalamus is regulated by both hormonally mediated signals (e.g., about:blank 223/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology negative feedback signals) and by neuronal input from a number of sources. Neuronal signals are mediated by neurotransmitters such as acetylcholine, dopamine, norepinephrine, serotonin, γ-aminobutyric acid (GABA), and opioids. Cytokines that are involved in immune and inflammatory responses, such as the interleukins, also are involved in the regulation of hypothalamic function. This is particularly true of the hormones involved in the hypothalamic–pituitary–adrenal axis. Thus, the hypothalamus can be viewed as a bridge by which signals from multiple systems are relayed to the pituitary gland.2,3 (Fig. 40.3). Figure 40.3 Control of hormone production by the hypothalamic– pituitary target cell feedback mechanism. Hormone levels from the target glands regulate the release of hormones from the anterior pituitary through a negative feedback system. The dashed line represents feedback control. Pituitary Hormones. The pituitary gland has been called the master gland because its hormones control the functions of many target glands and cells.2 Hormones produced by the anterior pituitary control body growth and metabolism (GH), function of the thyroid gland (TSH), glucocorticoid hormone levels (ACTH), function of the gonads (FSH and luteinizing hormone [LH]), and breast growth and milk production (prolactin). Hypothalamic releasing hormones regulate most of the pituitary hormones. GH secretion is stimulated by GHRH; TSH by TRH; ACTH by CRH; and LH and FSH by GnRH.2,3 Feedback Regulation Final exam content.Relationship between hypothalmus and pituitary gland PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 224/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 3/7/2023 Urine Tests Measurements of urinary hormone or hormone metabolite excretion often are done on a 24-hour urine sample and provide a better measure of hormone levels during that period compared to hormones measured in an isolated blood sample. In particular, a 24-hour urine sample for urinary cortisol levels is frequently performed in the diagnostic workup for Cushing syndrome.12 Hormone Stimulation and Suppression Tests Hormone stimulation tests are used when hypofunction of an endocrine organ is suspected. A tropic or stimulating hormone can be administered to test the capacity of an endocrine organ to increase hormone production. The capacity of the target gland to respond is measured by an increase in the appropriate hormone.2 For example, the function of the hypothalamic–pituitary–thyroid system can be evaluated through stimulation tests using TRH and measuring TSH response. Failure to increase TSH levels after a TRH stimulation test suggests an inadequate capacity to produce TSH by the pituitary (i.e., the pituitary is dysfunctional in some way). Suppression tests are used when hyperfunction of an endocrine organ is suspected. When an organ or tissue is functioning autonomously (i.e., it is not responding to the normal negative feedback control mechanisms and continues to secrete excessive amounts of hormone), a suppression test may be useful to confirm the situation.2 For example, when a GH- secreting tumor is suspected, the GH response to a glucose load is measured as part of the diagnostic workup. Normally, a glucose load would suppress GH levels. However, in adults with GH-secreting tumors (a condition known as acromegaly), GH levels are not suppressed.13 Genetic Testing Genetic testing is rapidly becoming an important approach for diagnosing selected endocrine disorders. Some endocrine-related disorders for which specific genetic pathophysiologic markers have been identified include X-linked hypophosphatemic rickets, epithelial thyroid carcinoma, hypopituitarism, familial pheochromocytoma and paraganglioma, multiple endocrine neoplasia types I and II, and certain disorders of short stature including Turner syndrome.2 Multiple endocrine neoplasia type II is an example of how genetic testing can be useful in diagnosing endocrine disorders. Development of this disorder has been connected with the RET protooncogene, which is located on the long arm of chromosome 10, at position 10q11.21.14 Persons who are believed to be at risk for multiple endocrine neoplasia type II can now be tested for the presence of the RET protooncogene. If genetic testing for the RET protooncogene is positive, the person can consider prophylactic treatment for some of the conditions that are characteristic of multiple endocrine neoplasia type II, which include medullary thyroid carcinoma and pheochromocytoma. A drawback to genetic testing is the cost, which at this point in the development of the technology, can still be quite expensive.2 Imaging Imaging studies are important in the diagnosis and follow-up of endocrine disorders. Imaging modalities related to endocrinology can be divided into nonisotopic and isotopic types. Nonisotopic imaging includes magnetic resonance imaging (MRI) and computed tomography (CT) scanning, both of which provide important information about structural changes within solid tissue. An advantage of MRI is that it PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created does not require the use of ionizing radiation (which is required for CT by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's scanning); disadvantages of MRI scanning include the long time prior permission. Violators will be prosecuted. needed to complete the scan. Many MRI scanners require the person about:blank 225/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology to be in an enclosed space for the long scanning time, which some individuals do not tolerate well. Open MRI scanners have been developed to respond to this concern. An issue that must be considered with CT scanning is the use of contrast agents. Nonradioactive iodine is often used as a contrast agent to enhance the quality of CT images. However, these iodine contrast preparations must be used with caution with persons with renal disease and allergies. Additionally, the previous use of nonradioactive iodine contrast material will interfere with the use of radioiodine imaging studies (discussed below) of the thyroid for approximately 4 weeks.2 Ultrasonographic scanning provides good structural imaging and has the advantages of providing a “real-time” image that does not use radioactive elements. Therefore, ultrasonography is frequently used to aid in visualization of a lesion for biopsy.2 Dual-electron x-ray absorptiometry (DEXA) is used routinely for the diagnosis and monitoring of osteoporosis and metabolic bone diseases.15 Isotopic imaging includes nuclear medicine imaging studies performed after administering a radioisotope, which is selectively taken up by the tissue being investigated (for example, radioiodine is taken up by the thyroid gland). Radioisotopes can be administered orally, intravenously, or by inhalation, depending upon the molecule being administered.2 Positron emission tomography (PET) scanning is another isotopic method, which is being used more widely in evaluating selected endocrine disorders, such as detecting the presence of metastatic thyroid cancers. PET scanning involves the administration of a short-lived radionuclide emitter of positrons in a form that is taken up by body tissues.2 PET scanning has expanded to PET/CT imaging in which both types of images are acquired almost simultaneously for enhanced detail and identification of previously difficult structures. The advantage of PET/CT is that the CT component allows a good examination of the tissue structure, whereas the PET component provides information about tissue function.16 PET/CT has been demonstrated to be useful in managing thyroid cancers.17 IN SUMMARY Exam Three. When would the health care provider order these diagnostic tests (which test for which disorder)? What would the provider order in suspected hypofunction? Hyperfunction? Important 8/16/2022 Assessment of Hypothalamic–Pituitary Function Hypothalamic-Pituitary Regulation. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 226/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 Glucocorticoids The glucocorticoid hormones, mainly cortisol, are synthesized in the zona fasciculata and the zona reticularis of the adrenal gland.4 The blood levels of these hormones are regulated by negative feedback mechanisms of the HPA system (Fig. 41.9). Just as other pituitary hormones are controlled by releasing factors from the hypothalamus, corticotropin-releasing hormone (CRH) is important in controlling the release of ACTH. Cortisol levels increase as ACTH levels rise and decrease as ACTH levels fall. There is considerable diurnal variation in ACTH levels, which reach their peak in the early morning (around 6 to 8 am) and decline as the day progresses. This appears to be due to rhythmic activity in the CNS, which causes bursts of CRH secretion and, in turn, ACTH secretion. This diurnal pattern is reversed in people who work during the night and sleep during the day. The rhythm may also be changed by physical and psychological stresses, endogenous depression, manic- depressive psychosis, and liver disease or other conditions that affect cortisol metabolism.4 Figure 41.9 The HPA feedback system that regulates glucocorticoid (cortisol) levels. Cortisol release is regulated by ACTH. Stress exerts its effects on cortisol release through the HPA system and CRH, which controls the release of ACTH from the anterior pituitary gland. Increased cortisol levels incite a negative feedback inhibition of ACTH release. The glucocorticoids perform a necessary function in response to stress and are essential for survival. When produced as part of the stress response, these hormones aid in regulating the metabolic functions of the body and in controlling the inflammatory response. The actions of cortisol are summarized in Table 41.4. Many of the anti-inflammatory actions attributed to cortisol result from the administration of pharmacologic levels of the hormone.4 TABLE 41.4 ACTIONS OF CORTISOL Important 1/19/2023 Glucocorticoid Hormone Excess (Cushing Syndrome) Exam three content. Glucocorticoid hormone excess. Cushing syndrome clinical presentation. Important 8/16/2022 Clinical Manifestations PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 227/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 The major manifestations of Cushing syndrome represent an exaggeration of the many actions of cortisol (see Table 41.4). Altered fat metabolism causes a peculiar deposition of fat characterized by a protruding abdomen; subclavicular fat pads or “buffalo hump” on the back; and a round, plethoric “moon face” (Figs. 41.12 and 41.13). There is muscle weakness, and the extremities are thin because of protein breakdown and muscle wasting. In advanced cases, the skin over the forearms and legs becomes thin, having the appearance of parchment. Purple striae, or stretch marks, from stretching of the catabolically weakened skin and subcutaneous tissues are distributed over the breast, thighs, and abdomen. Osteoporosis may develop because of destruction of bone proteins and alterations in calcium metabolism, resulting in back pain, compression fractures of the vertebrae, and rib fractures. As calcium is mobilized from bone, renal calculi may develop.1,2,8 Important 8/25/2022 This causes hypokalemia, as a result of excessive potassium excretion, and hypertension, resulting from sodium retention. Important 8/25/2022 Inflammatory and immune responses are inhibited, resulting in increased susceptibility to infection. Cortisol increases gastric acid secretion, which may provoke gastric ulceration and bleeding. An accompanying increase in androgen levels causes hirsutism, mild acne, and menstrual irregularities in women. Excess levels of the glucocorticoids may give rise to extreme emotional lability, ranging from mild euphoria and absence of normal fatigue to grossly psychotic behavior.1,2,8 Important 8/25/2022 Diagnosis of Cushing syndrome is a two-step process: the first step is the diagnosis of hypercortisolism, and the second step is testing to determine the cause of the cortisol hypersecretion. Important 8/25/2022 Untreated, Cushing syndrome produces serious morbidity and even PRINTED BY: [email protected]. Printing of Notes and death. Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 228/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 The choice of surgery, irradiation, or pharmacologic treatment is determined largely by the cause of the hypercortisolism. The goal of treatment for Cushing syndrome is to remove or correct the source of hypercortisolism without causing permanent pituitary or adrenal damage. Transsphenoidal removal of a pituitary adenoma or a hemihypophysectomy is the preferred method of treatment for Cushing disease. Important 8/25/2022 Incidental Adrenal Mass FYI: Interesting reading, helpful for understanding the significance of finding an incidentaloma, requires further investigation into causes. Important 8/16/2022 Glucocorticoid Hormones Important 1/19/2023 DIABETES MELLITUS AND THE METABOLIC SYNDROME Exam three. Effect of stress on clients with diabetes. Counter- regulatory hormones. Glucocorticoid hormones. Important 8/16/2022 Type 1 Diabetes Mellitus PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 229/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 Type 2 Diabetes Mellitus and the Metabolic Syndrome Type 2 DM accounts for the majority of cases of diabetes, approximately 90% to 95%.55 It is a heterogeneous condition that describes the presence of hyperglycemia in association with relative insulin deficiency. Many people with type 2 diabetes are adults and overweight; however, recent trends indicate that type 2 diabetes has become a more common occurrence in adolescents and children with obesity, a condition termed MODY.52 Although autoimmune destruction of the beta cells does not occur, people with type 2 diabetes eventually may require insulin. Therefore, the previous terms related to type 2 diabetes, such as adult-onset diabetes and non–insulin-dependent diabetes, can generate confusion and are thus obsolete.55 Type 2 diabetes has a strong genetic component. A number of genetic and acquired pathogenic factors have been implicated in the progressive impairment of beta-cell function in people with prediabetes and type 2 diabetes.52,63 The metabolic abnormalities associated with type 2 diabetes are illustrated in Figure 41.18. These abnormalities include: Figure 41.18 Pathogenesis of type 2 DM. 1. Insulin resistance 2. Deranged secretion of insulin by the pancreatic beta cells 3. Increased glucose production by the liver52,55,63 In contrast to type 1 diabetes, where absolute insulin deficiency is present, people with type 2 diabetes can have high, normal, or low insulin levels. Insulin resistance is the decreased ability of insulin to act effectively on target tissues, especially muscle, liver, and fat. It is the predominate characteristic of type 2 diabetes and results from a combination of factors such as genetic susceptibility and obesity.52,55,63 Table 41.8 compares the characteristics of type 1 and type 2 DM. Final exam content. Type 2 DM and metabolic syndrome PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 230/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 Insulin resistance initially stimulates an increase in insulin secretion, often to a level of modest hyperinsulinemia, as the beta cells attempt to maintain a normal blood glucose level. In time, the increased demand for insulin secretion leads to beta-cell exhaustion and failure. This results in elevated postprandial blood glucose levels and an eventual increase in glucose production by the liver. Because people with type 2 DM do not have an absolute insulin deficiency, they are less prone to ketoacidosis compared to people with type 1 diabetes.52,55,63 In type 2 DM, the basal hepatic insulin resistance is manifested by a hepatic overproduction of glucose despite a fasting hyperinsulinemia, with the rate of glucose production being the primary determinant of the elevated FPG in people with type 2 diabetes. Although the insulin resistance seen in people with type 2 diabetes can be caused by a number of factors, it is strongly associated with obesity and physical inactivity.1,2,52,55,63 Specific causes of beta-cell dysfunction in type 2 DM are unclear; however, it appears that in both type 1 DM and type 2 DM, there may be an increased apoptosis of pancreatic beta cells in response to the stress of hyperglycemia.63 Insulin Resistance and the Metabolic Syndrome. Increasing evidence indicates that insulin resistance not only contributes to the hyperglycemia in people with type 2 diabetes, but it also may play a role in other metabolic abnormalities. These include obesity, high levels of plasma triglycerides and low levels of high- density lipoproteins (HDL), hypertension, systemic inflammation (as detected by C-reactive protein [CRP] and other mediators), abnormal fibrinolysis, abnormal function of the vascular endothelium, and macrovascular disease (coronary artery, cerebrovascular, and peripheral arterial disease). This constellation of abnormalities is often referred to as the insulin resistance syndrome, syndrome X, or, the preferred term, metabolic syndrome.1,2,52,55,63 The clinical signs, laboratory abnormalities, and associated illnesses associated with this syndrome are described in Chart 41.5. Important 8/25/2022 he net results of the combined systemic inflammation, increased oxidative stress, endothelial dysfunction, and increased blood lipids all contribute to the constellation of metabolic alterations that are present in the metabolic syndrome—including dyslipidemia, hypertension, vascular pathology, and abnormal coagulation.64 Important 8/16/2022 Clinical Manifestations of Diabetes Mellitus PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 231/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/16/2022 Acute Complications of Diabetes Important 1/19/2023 Diabetic Ketoacidosis Exam three content. DKA Important 8/25/2022 DKA most commonly occurs in a person with type 1 diabetes in whom the lack of insulin leads to increased release of fatty acids from adipose tissue because of the unsuppressed adipose cell lipase activity that breaks down triglycerides into fatty acids and glycerol. The increase in fatty acid levels leads to ketone production by the liver (Fig. 41.19). DKA can occur at the onset of the disease, often before diagnosis, and can occur as a complication during the course of the disease. Important 3/6/2023 Stress increases the release of gluconeogenic hormones and predisposes the person to the development of ketoacidosis. DKA is often preceded by physical or emotional stress, such as infection or inflammation, pregnancy, or extreme anxiety. In clinical practice, ketoacidosis also occurs with the omission or inadequate use of insulin.1,2,4 Exam 3 content PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 232/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/25/2022 Clinical Manifestations. A day or more of polyuria, polydipsia, nausea, vomiting, and marked fatigue, with eventual stupor that can progress to coma commonly precedes DKA. Abdominal pain and tenderness may be experienced without abdominal disease. The breath has a characteristic fruity smell because of the presence of the volatile keto acids. Hypotension and tachycardia may be present because of a decrease in blood volume. A number of the signs and symptoms that occur in DKA are related to compensatory mechanisms. The heart rate increases as the body compensates for a decrease in blood volume, and the rate and depth of respiration increase (i.e., Kussmaul respiration) as a compensatory mechanism to prevent further decrease in pH.1,2,4 Important 8/16/2022 Hyperosmolar Hyperglycemic State Hyperosmolar hyperglycemic state and fluid volume imbalance causes. Important 1/19/2023 Diabetic Complications Related to Counter-Regulatory Mechanisms The counter-regulatory mechanisms described above are associated with several patterns of diabetic complications, known as the Somogyi effect and the dawn phenomenon. Exam three content. Effect of stress on clients with diabetes. Counter-regulatory hormones. Glucocorticoid hormones. Important 8/16/2022 The Somogyi Effect PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 233/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/19/2022 n people with DM, the insulin-induced hypoglycemia produces a compensatory increase in blood levels of counter-regulatory hormones such as catecholamines, glucagon, cortisol, and GH. These counter-regulatory hormones cause blood glucose to become elevated and produce some degree of insulin resistance. The cycle begins when the increase in blood glucose and insulin resistance is treated with larger insulin doses. Important 8/19/2022 hypoglycemic episode often occurs during the night Important 8/19/2022 When a Somogyi situation is suspected, people may be asked to test blood sugars in the middle of the night to identify possible hypoglycemia.66 Important 8/16/2022 The Dawn Phenomenon Important 8/19/2022 increased fasting blood glucose and/or insulin requirements during the early morning hours that are not triggered by a preceding hypoglycemic event Important 8/19/2022 The dawn phenomenon is the result of circadian variations in hormone secretion, with glucagon secretion to release energy stores in preparation for the activity of the day. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 234/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/19/2022 Chronic Complications of Diabetes Mellitus Diabetes is a disease that many of you will encounter in the rural setting. Often, you will diagnose theis condition for the first time in your rural patients. For this reason you need a strong foundation in this disease. Important 8/19/2022 disorders of the microvasculature Important 8/19/2022 disorders of gastrointestinal motility, Important 8/19/2022 macrovascular complications Important 8/19/2022 foot ulcers Important 8/19/2022 People with diabetes are also more susceptible to infections. Important 8/19/2022 level of chronic hyperglycemia is the best predictive factor for diabetic complications Important: chronic hyperglycemia is the best predictive factor for diabetic complications. It is essential to teach patients how to prevent these complications (diet, exercise, and especially PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created important---medications). by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 235/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/19/2022 Figure 41.20 Long-term complications of DM. Figure 41.20 summarizes the chronic complications well. Important 1/19/2023 Microvascular Complications Exam three content Important 8/19/2022 advanced glycation end products AGEs develop from chronic hyperglycemia which leads to inflammation and vessel damage. Important 8/19/2022 as reflected in the hemoglobin A1C measure. A Important 8/19/2022 GEs induce vascular damage Important 8/19/2022 damage endothelial cells Important 8/19/2022 AGEs may be compounded by the increased oxidative stress, chronic systemic inflammation, and dyslipidemia PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 236/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/19/2022 associated with the metabolic syndrome Important 8/19/2022 The types of microvascular complications that occur in DM can include neuropathy, retinopathy, nephropathy, and disorders of gastrointestinal motility. Important 8/19/2022 In the United States, diabetes is a leading cause of vision loss and blindness as well as chronic kidney disease.1,2 Important 8/19/2022 Macrovascular Complications Important 8/19/2022 people with DM are at increased risk of macrovascular complications such as coronary artery disease, cerebrovascular disease and stroke, and peripheral vascular disease. Important 8/19/2022 KEY POINTS CHRONIC COMPLICATIONS OF DIABETES This box provides an excellent bullet point summary. Important 8/19/2022 Diabetic Foot Ulcers Foot problems are common among people with diabetes and may become severe enough to cause ulceration, infection, and, eventually, the need for amputation. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created Diabetic foot ulcers are the result of microvascular complications. by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 237/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 8/19/2022 Infections Infections are a primary concern to people with diabetes Important 8/19/2022 The presence of chronic vascular complications contributes to suboptimal response to infection in a person with diabetes, as do hyperglycemia and altered neutrophil function. Important 8/19/2022 Vascular disease may impair circulation and delivery of blood cells and other necessary substances for promotion of adequate inflammatory response and effective healing. Hyperglycemia and glycosuria may influence the growth of microorganisms and increase severity of infections.1,2,4 Important 1/19/2023 REVIEW EXERCISES Practice your diagnostic reasoning by reading these cases and determining the top diagnoses. Important 8/25/2022 Testicular Cancer Testicular cancer accounts for 1% of all male cancers.2 It is relatively rare. However, testicular cancer is the most common cancer in young men between 15 and 35 years of age. The incidence of testicular tumors has doubled in the past 40 years. The 5-year survival rate exceeds 95%, and after treatment, most survivors can expect a near-normal life expectancy.30 Important 8/25/2022 The risk factors include cryptorchidism, genetic factors, and disorders of testicular development.2 The strongest association has been with cryptorchid testis. Genetic predisposition also appears to be important. Family clustering of the disorder has been described, PRINTED BY: [email protected]. Printing of Notes and although a well-defined pattern of inheritance has not been Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this established. book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 238/288 7/19/24, 6:06 PM Highlights & Notes: Lippincott CoursePoint for Norris: Porth's Pathophysiology Important 1/19/2023 Clinical Manifestations and Diagnosis. Often the first sign of testicular cancer is a slight enlargement of the testicle that may be accompanied by some degree of discomfort. This may be an ache in the abdomen or groin or a sensation of dragging or heaviness in the scrotum.27 Testicular cancer can spread when the tumor may be barely palpable. Signs of metastatic spread include swelling of the lower extremities, back pain, neck mass, cough, hemoptysis, or dizziness. The diagnosis of testicular cancer requires a thorough urologic history and physical examination. A painless testicular mass may be cancer. Conditions that produce an intrascrotal mass similar to testicular cancer include epididymitis, orchitis, hydrocele, or hematocele. The examination for masses should include palpation of the testes and surrounding structures, transillumination of the scrotum, and abdominal palpation. Testicular ultrasonography can be used to differentiate testicular masses. CT scans and MRI are used in assessing metastatic spread. Tumor markers that measure protein antigens produced by malignant cells provide information about the existence of a tumor and the type of tumor present. These markers may detect tumor cells that are too small to be found on physical examination or radiographs. Two tumor markers are useful in evaluating the tumor response to therapy: α-fetoprotein, a glycoprotein that is normally present in fetal serum in large amounts and beta-human chorionic gonadotropin (beta-hCG), a hormone that is normally produced by the placenta in pregnant women.31 During embryonic development, the totipotential germ cells of the testes travel down normal differentiation pathways and produce different protein products. The reappearance of these protein markers in the adult suggests activity of undifferentiated cells in a testicular germ cell tumor. The clinical staging (TNM classification) for testicular cancer is as follows: stage I, tumor confined to testes, epididymis, or spermatic cord; stage II, tumor spread to retroperitoneal lymph nodes below the diaphragm; and stage III, metastases outside the retroperitoneal nodes or above the diaphragm.9 Staging procedures include CT scans of the chest, abdomen, and pelvis; ultrasonography for detection of bulky inferior nodal metastases; and occasionally lymphangiography. Exam three content. PRINTED BY: [email protected]. Printing of Notes and Highlights is for personal, private use only. Notes created by user are not part of publisher content. No part of this book may be reproduced or transmitted without publisher's prior permission. Violators will be prosecuted. about:blank 239/288