Endocrine Disorders PDF

Pathophysiology (2) (MBS 253) Lecture 10 Endocrine disorders A-Insulin and Diabetes Mellitus B-Parathyroid Hormone and Calcium Textbook ;Pathophysiology for the Health Professions, 4th edition, 2011 Chapter 25 (p.545-572)  Endocrine Diso...

Pathophysiology (2) (MBS 253) Lecture 10 Endocrine disorders A-Insulin and Diabetes Mellitus B-Parathyroid Hormone and Calcium Textbook ;Pathophysiology for the Health Professions, 4th edition, 2011 Chapter 25 (p.545-572)  Endocrine Disorders Chapter outline Review of the Endocrine System Endocrine Disorders Insulin and Diabetes Mellitus – Comparison of Type 1 and Type 2 Diabetes Parathyroid Hormone and Calcium Pituitary Hormones Growth Hormone Antidiuretic Hormone (Vasopressin) – Diabetes Insipidus – Inappropriate ADH Syndrome Thyroid Disorders – Goiter – Hyperthyroidism (Graves’ Disease) – Hypothyroidism – Diagnostic Tests Adrenal Glands – Adrenal Medulla – Adrenal Cortex – Cushing’s Syndrome – Addison’s Disease  Endocrine Disorders After studying this chapter, the student is expected to: 1. Explain how hormone levels in the blood are controlled by negative feedback or by the hypothalamic-pituitary system under normal and abnormal conditions. 2. Explain the relationship between metabolic syndrome and diabetes mellitus. 3. Differentiate Type 1 and Type 2 diabetes mellitus. 4. Explain the early signs of diabetes. 5. Compare the causes and development of hypoglycemia and hyperglycemia. 6. Describe the common degenerative effects of diabetes mellitus. 7. Explain the relationship between parathyroid hormone and calcium and their changes with various disorders.  REVIEW OF THE ENDOCRINE SYSTEM The major endocrine glands are scattered throughout the body and include the pituitary gland (hypophysis), the two adrenal glands, the thyroid gland, the four parathyroid glands, the endocrine portion of the pancreas, the gonads, the pineal gland, and the thymus Endocrine glands secrete hormones directly into the blood, in contrast to exocrine glands that secrete into a duct, such as mucous glands or pancreatic digestive enzymes. FIGURE 25-1 Location of the endocrine glands.  Hormones Hormones are chemical messengers, can be classified by: – Action; control hormone levels or blood glucose and calcium levels – Source; endocrine organ – Chemical structure amino acid derivatives the lipid cholesterol, steroids Peptides or proteins are synthesized, Following release from an endocrine gland, the hormones circulate to target cells in other glands or tissues. After acting on specific receptors on or in the target cells, the hormones are metabolized or inactivated by the target tissues or the liver and excreted by the kidneys  Hormones What is the major mechanism that controls hormone levels in the blood ? Negative feedback mechanism – For example, as levels of glucose increase, the secretion of insulin increases. When glucose levels decrease, insulin secretion decreases. FIGURE 25-2 Negative feedback mechanism with glucose and insulin and glucagon.  Hormones The endocrine and nervous systems work together to regulate metabolic activities. – Some hormones are controlled by the nervous system through the hypothalamus (e.g., epinephrine and norepinephrine). Together, the hypothalamus and pituitary gland comprise a more complex control system for some hormones. – The hypothalamus initially secretes releasing or inhibiting hormones; for example, thyrotropin-releasing factor (TRF) acts on the pituitary gland to secrete thyroid-stimulating hormone (TSH).  Hormones When determining the cause of a hormonal deficit or excess, it is necessary to check pituitary hormone levels as well as those of the target gland – For example, a deficit of thyroxine could result from a pituitary problem (decreased secretion of TSH) or a problem in the thyroid gland. In the latter case, blood levels of TSH would be high, whereas thyroxine levels would be low  Hormones In some cases, secretion is controlled by more than one mechanism (e.g., aldosterone is regulated by renin secretion and serum levels of Na+ and K+). Another variable affecting hormone levels in the body is the rate or timing of secretion. – Some hormones, such as thyroid hormone, are maintained at fairly constant levels, – whereas others are released in large amounts intermittently as the demand occurs. – Some hormones, such as estrogen, follow a cyclic pattern in women. – ACTH and cortisol are secreted in a diurnal pattern, the highest levels occurring in the morning and the lowest levels at night. If an individual’s sleep pattern changes, the hormonal secretion changes with it. However, any acute stress leads to the sympathetic nervous system (SNS) overriding this pattern, resulting in a great outflow of ACTH and cortisol.  ENDOCRINE DISORDERS All disorders reflect impaired control/feedback and result in hormone levels that are too high or too low (problems with effects) Two categories of endocrine problems Excessive amount of hormone Deficit amount of hormone  Most Common Causes of Endocrine Disorders Excess hormone level – Benign tumor, or adenoma. – Excretion by liver and kidney is impaired – Congenital defects produce excess hormone Deficit of hormone level or reduced effects – Destructive tumor produce too little hormone – Receptors of target cells are resistant or insensitive to the hormone, thus creating the effect of a hormone deficit. This lack of response may result from a genetic defect, an autoimmune response, or excessive demand on the target cells. – Abnormal immune reactions, – Atrophy or surgical removal of the gland – Antagonistic hormone production is increased – Congenital defects.  Diagnostic tests Blood tests , – check the serum level of a hormone – use of radioimmunoassay (RIA) methods – immunochemical methods). – The effectiveness of a hormone can be measured, – blood glucose or blood calcium levels may reflect the activity of the respective hormones. In some patients, an excessive amount of hormone may arise from an ectopic (outside) source, such as a bronchogenic cancer, rather than from a gland. In such cases, the levels of tropic hormones are low.  Diagnostic tests Urine tests: Twenty-four-hour are helpful for ascertaining daily levels of hormones or their metabolites rather than using a random level taken at a specific moment. Stimulation or suppression tests: Can be performed to confirm the hyper-function or hypo- function of a gland. Scans, ultrasound, and magnetic resonance imaging (MRI): are also helpful for checking the location and type of lesion that may be present. Biopsy : Is essential to eliminate the possibility of malignancy  INSULIN AND DIABETES MELLITUS Diabetes mellitus is caused by ; – Decreased secretion of insulin from the beta cells in the islets of Langerhans or – Lack of response by cells to insulin (insulin resistance). – Production of insulin antagonist Insulin is an anabolic hormone Deficient insulin results in abnormal carbohydrate, protein, and fat metabolism – Transport of glucose and amino acids into cells is impaired, as well as the synthesis of protein and glycogen. – Many tissues and organs in the body are adversely affected by diabetes. – Some types of cells are not affected directly by the deficit of insulin.  INSULIN AND DIABETES MELLITUS Some tissue can transport glucose in the absence of insulin – Brain cells. This is fortunate, because neurons require glucose constantly as an energy source. – Digestive tract, insulin is not required for glucose absorption. – Exercising skeletal muscle can utilize glucose without proportionate amounts of insulin. This can be significant because excessive exercise can deplete blood glucose and result in hypoglycemia. Conversely, exercise is helpful in controlling blood glucose levels in the presence of an insulin deficit. – Kidney and myocardium  Types of Diabetes Mellitus There are two basic types of diabetes: types 1 and 2 Type1 Insulin dependent diabetes mellitus (IDDM), or juvenile diabetes, the more severe form. Type2 diabetes, formerly referred to as noninsulin dependent diabetes mellitus (NIDDM), or mature-onset diabetes, milder form. Gestational diabetes may develop during pregnancy and disappear after delivery of the child  Type1: IDDM or Juvenile Diabetes It occurs more frequently in children and adolescents but can develop at any age. It results from destruction of the pancreatic beta cells in an autoimmune reaction, resulting in an absolute deficit of insulin in the body and therefore requiring replacement therapy. The amount of insulin required is equivalent to the metabolic needs of the body based on dietary intake and metabolic activity. Acute complications such as hypoglycemia or ketoacidosis are more likely to occur in this group. A major factor predisposing to strokes (cerebrovascular accident, CVA), heart attacks (myocardial infarction, MI), peripheral vascular disease, and amputation, kidney failure, and blindness.  Type2: NIDDM, or Mature-Onset Diabetes It is based on decreased effectiveness of insulin or a relative deficit of insulin. Caused by: 1- decrease pancreatic beta cell production of insulin 2- increased resistance by body cells to insulin, 3- increased production of glucose by the liver, or a combination of these factors. Controlled by adjusting the need for insulin by: 1- Regulating dietary intake 2- Increasing the use of glucose, such as with exercise 3- Reducing insulin resistance 4- Stimulating the beta cells of the pancreas to produce more insulin  Type2: NIDDM, or Mature-Onset Diabetes Type 2 is a milder form of diabetes Often developing gradually in older adults, the majority of whom are overweight. However, increased incidence occur in adolescents and younger adults with metabolic syndrome, a complex of several pathophysiologic conditions marked by obesity, cardiovascular changes, and significant insulin resistance due to increased adipose tissue. The prevalence of type 2 diabetes increases with age, with approximately half the cases found in persons older than 55 years of age.  Types of Diabetes Mellitus with metabolic syndrome any age. Of beta cells genetic (Decrease insulin secretion or increase resistance) metabolic syndrome: a complex of obesity, cardiovascular changes, and significant insulin resistance due to increased adipose tissue  Pathophysiology An insulin deficit leads to the following sequence of events. Initial Stage. 1. Decreased transportation and use of glucose Lack of nutrients entering the cells stimulates appetite (polyphagia & fatigue) 2. Blood glucose levels rise (hyperglycemia). 3. Excess glucose spills into the urine (glucosuria) 4. Glucose in the urine exerts osmotic pressure in the filtrate, resulting in a large volume of urine to be excreted (polyuria), with the loss of fluid and electrolytes (e.g., sodium and potassium) from the body tissues. 5. Fluid loss through the urine and high blood glucose levels draw water from the cells, resulting in dehydration 6. Dehydration causes thirst (polydipsia). 7. Lack of nutrients entering the cells stimulates appetite (polyphagia)  Pathophysiology Progressive Effects: metabolic changes If the insulin deficit is severe or prolonged, the process continues to develop 8. Lack of glucose in cells results in catabolism of fats and proteins, excessive amounts of fatty acids and their metabolites, known as ketones or ketoacids, in the blood. (ketoacidosis) – The ketoacids bind with bicarbonate buffer in the blood, leading to decreased serum bicarbonate and eventually to a decrease in the pH of body fluids. (Note that ketones can also accumulate in people on starvation diets.) 9. Ketoacids are excreted in the urine (ketonuria). 10. As dehydration develops, glomerular filtration rate drops, resulting in decompensated metabolic acidosis, which has life threatening potential (diabetic ketoacidosis [DKA] or diabetic coma).  Pathophysiology Diabetic ketoacidosis [DKA] occurs more frequently in untreated or uncontrolled Type 1 diabetes. The lack of glucose in cells results in catabolism of fats, leading to excessive buildup of fatty acids and their metabolites, ketoacids  Signs and symptoms As Type 2 diabetes develops, weight gain or increased abdominal girth is common, whereas in Type 1 weight loss is common. As blood glucose rises in the early stage, fluid loss is significant. Polyuria is indicated by urinary frequency, which is often noticed by the patient at night (nocturia) with the excretion of large volumes of urine. Thirst and dry mouth occur in response to fluid loss. Fatigue and lethargy develop. Weight loss may follow. Appetite is increased. Typically, the three Ps— polyuria, polydipsia, and polyphagia—herald the onset of diabetes. If the insulin deficit continues, the patient progresses to the stage of diabetic ketoacidosis.  Diagnostic tests 1. Fasting blood glucose level, 2. Glucose tolerance test, 3. Glycosylated hemoglobin test are used to screen people with clinical and subclinical diabetes. – At present, a fasting blood sugar equal to or greater than 126 mg/dL, taken on more than one occasion, confirms a diagnosis of diabetes. – Glycosylated hemoglobin (HbA1c) monitor blood glucose levels over several months (long time control). The test should be repeated every 3 months. The acceptable level for HbA1c has been lowered to 6% (normal), so as to reduce the serious long-term effects of hyperglycemia.  Diagnostic tests Patients with diabetes can monitor themselves at home by taking a sample of capillary blood from a finger and checking it with a portable monitoring machine (glucometer). – When performed regularly, this self-monitoring test helps reduce the fluctuations in blood glucose levels and therefore the risk of complications. Urine tests for ketones are helpful for those who are predisposed to ketoacidosis. Arterial blood gas analysis is required if ketoacidosis develops. Serum electrolytes may be checked as well.  Treatment Maintenance of normal blood glucose levels is important to minimize the complications of diabetes mellitus, both acute and chronic. Glucose intake must be balanced with use. Treatment measures depend on the severity of the insulin deficit and may change over time. There are essentially three levels of control: 1. Diet and exercise 2. Oral medication to increase insulin secretion or reduce insulin resistance 3. Insulin replacement Diet Therapy is based on maintaining optimum body weight as well as control of blood glucose levels. This is important for persons with both types of diabetes. Recommended diets include:  More complex carbohydrates with a low glycemic index in contrast to simple sugars, which have a high glycemic index and elevate blood glucose rapidly.  Adequate protein.  low cholesterol and low lipid levels.  Increased fiber with meals appears to reduce surges in blood sugar associated with food intake. Exercise A regular moderate exercise program is very beneficial to the diabetic. Exercise can increase the uptake of glucose by muscles substantially without an increase in insulin use. It assists in weight control, reduces stress, and improves cardiovascular fitness. There is a risk that hypoglycemia may develop with exercise, particularly strenuous or prolonged exercise. The increased use of glucose by skeletal muscle, plus the increased absorption of insulin from the injection site, may lower blood glucose levels precipitously. Increasing carbohydrate intake by eating a snack to compensate for exercise can decrease this risk. Oral Medications Metformin (Glucophage) is usually the first medication prescribed in the treatment of type 2 diabetes when diet and exercise alone are not effective; it reduces insulin resistance and glucose production. Sulfonylureas such as glyburide help the body to create more insulin. Others as: Meglitinides, Thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors. Frequently a combination of diet, exercise, and oral hypoglycemic drugs is effective in treating mild forms of diabetes. Insulin Replacement It must be injected subcutaneously because it is a protein that is destroyed in the digestive tract if taken orally. The primary form of insulin used now is a biosynthetic form of insulin, identical to human insulin (Humulin), synthesized by bacteria using recombinant DNA techniques. Insulin is standardized in units for subcutaneous administration.. Blood glucose levels should be checked at frequent intervals.  Complications Are directly related to duration and extent of abnormal blood glucose levels Many factors lead to fluctuations in SGLs – Variations of diet – Change in physical activity – Infection – Vomiting Acute Complications Hypoglycemia (insulin shock). Diabetic ketoacidosis Hyperosmolar hyperglycemic nonketotic coma Chronic Complications Vascular problems Neuropathy. Cataracts.  Acute Complications Hypoglycemia (insulin shock). Cause; excess insulin in blood It usually occurs in patients with Type 1 diabetes, or with insulin replacement therapy Can occur with excess oral drugs Often following: – strenuous exercise, – an error in dosage, – vomiting, – skipping a meal after taking insulin Hypoglycemia (insulin shock). Signs and symptoms: The manifestations of hypoglycemia are related directly to the low blood glucose levels, not to the high insulin levels. S/S are related to: 1- Impaired neurologic function; poor concentration, slurred speech , lack of coordination, and staggering gait. 2- Stimulating the sympathetic nervous system; increased pulse; pale, moist skin; anxiety; and tremors Treatment Immediate administration of a concentrated carbohydrate, such as sweetened fruit juice or candy. If the person is unconscious, glucose or glucagon may be given parenterally (usually intravenously). Hypoglycemia can be life threatening or can cause brain damage if it is not treated promptly..  Diabetic ketoacidosis results from insufficient insulin, – which leads to high blood glucose levels and mobilization of lipids to meet cellular needs results in production of ketoacids. more common in Type 1 patients, insulin dependent patients. Ketoacidosis usually develops over a few days may be initiated by – an infection or stress, which increases the demand for insulin in the body May result from an error in dosage or change of diet or alcohol intake Signs and symptoms : – related to dehydration, – metabolic acidosis, and – Electrolyte imbalances 1- Signs of dehydration thirst; dry, rough oral mucosa; warm, dry skin. The pulse is rapid but weak, blood pressure is low as the vascular volume decreases. 2- Rapid, deep respirations (Kussmaul’s respirations) and acetone breath (a sweet, fruity smell). -Lethargy and decreased responsiveness indicate depression of the central nervous system owing to acidosis and decreased blood flow. 3-Metabolic acidosis develops as ketoacids bind with bicarbonate ions in the buffer, leading to decreased serum bicarbonate levels and decreased serum pH. -As dehydration progresses, renal compensation reduced, acidosis becomes decompensated resulting in loss of consciousness. 4- Electrolyte imbalances include imbalances of sodium, potassium, and chloride. Signs include primarily abdominal cramps, nausea, and vomiting, as well as lethargy and weakness. Serum sodium is often low, but the potassium concentration may be elevated because of acidosis If the condition remains untreated, central nervous system depression develops owing to the acidosis and dehydration, leading to coma  Treatment of Diabetic ketoacidosis Administration of insulin as well as replacement of fluid and electrolytes. – Serum potassium levels may decrease when insulin is administered because insulin promotes transport of potassium into cells. Bicarbonate administration is essential to reverse the acidosis, Specific treatment to resolve the causative factor of the diabetic ketoacidosis episode. Hyperosmolar hyperglycemic nonketotic coma (HHNC) Occurs with Type 2 diabetes. Often the patient is an older person with an infection Onset is insidious and difficult to diagnose initially. Manifestations : Hyperglycemia and dehydration develop because of the relative insulin deficit, – but sufficient insulin is available to prevent ketoacidosis. Severe cellular dehydration with electrolytes disturbances results in; – neurologic deficits, – muscle weakness, – difficulties with speech, – abnormal reflexes  Chronic Complications Vascular problems: – Increased incidence of atherosclerosis changes may occur in both the small and large arteries because of degeneration related to the metabolic abnormalities associated with diabetes Microangiopathy Macroangiopathy Infections Cataracts. Complications of pregnancy  Vascular Problems 1- Microangiopathy: Capillary basement membrane becomes thick and hard, causing: Obstruction or rupture of capillaries and small arteries, It results in tissue necrosis and loss of function. Retinopathy is a leading cause of blindness Diabetic nephropathy, or vascular degeneration in the kidney glomeruli, eventually leads to chronic renal failure It is responsible for 40% of patients in end stage renal failure. Peripheral neuropathy: common complication due to ischemia in microcirculation in the peripheral nerves. Neuropathy Peripheral neuropathy is a common problem for diabetics. This leads to impaired sensation, numbness, tingling, weakness, and muscle wasting. It results from ischemia and altered metabolic processes. Degenerative changes occur in both unmyelinated and myelinated nerve fibers. The risks of tissue trauma and infection are greatly increased when vascular impairment and sensory impairment coexist. Autonomic nerve degeneration develops as well, leading to bladder incontinence, impotence, and diarrhea. Impaired vasomotor reflexes may cause dizziness when a person stands up.  Vascular Problems 2- Macroangiopathy: Affects the large arteries Result of high lipid levels like atherosclerosis – a high incidence of heart attacks, strokes, and peripheral vascular disease – Peripheral vascular disease also causes intermittent claudication (pain with walking), which greatly impairs mobility – May results in ulcers on the feet and legs that are slow to heal – Frequent infections and gangrenous ulcers – Amputation may be necessary  Infections More common in diabetes because of the vascular impairment, which decreases tissue resistance. Wound healing is slow, predisposing to infection in case of trauma or surgery. Diabetics are also susceptible to tuberculosis, which is increasing in incidence. Infections in the feet and legs due to vascular and neurological impairment. Fungal infections such as Candida occur frequently and persist on the skin in body folds, in the oral cavity and vagina.  Infections The urinary tract is a common site of infection, particularly if bladder function is compromised, and predisposes the patient to cystitis and pyelonephritis. Periodontal disease (infection in the tissues around the teeth) and dental caries (infection and decay in teeth) are much more common in diabetics.  Cataracts Clouding of the lens of the eye – degenerative process related to the abnormal metabolism of glucose, and it results in accumulated sorbitol and water in the lens, destroying the transparency. Cataracts may eventually lead to blindness and should be removed when they impair visual function  Complications of Pregnancy Complications for both the mother and fetus may occur during pregnancy. Maternal diabetes may become more severe, control is more difficult with the continual hormonal and metabolic changes. Increased incidence of spontaneous abortions and abnormalities in infants born to diabetic mothers. Infants born to diabetic mother show – increased size and weight for date – May experience hypoglycemia in first hours postnatally Potential complications of diabetes mellitus  Control of type 2 diabetes Diet containing – Increased fiber – Reduce lipids and simple glucose Regular exercise to reduce glucose levels Reduce insulin resistance by reducing body mass index (BMI) to normal level Monitoring blood glucose level Medications to stimulate B-cells to secret insulin If insulin dependent, proper administration of insulin to maintain glucose level in normal range Routine follow up and blood testing  Q. Identify the etiology of Diabetes mellitus List the predisposing factors for developing diabetes mellitus? PARATHYROID HORMONE AND CALCIUM  Hypoparathyroidism May be caused by – Tumor – Congenital lack of the four parathyroid glands, – Surgery or radiation in the neck region, – Autoimmune disease. Leads to hypocalcemia, or low serum calcium levels, resulting in: – Weak cardiac muscle contractions – Increase the excitability of nerves, leading to spontaneous contraction of skeletal muscle. – This causes muscle twitching and spasms, commonly known as tetany, which is usually observed first in the face and hands. Hypocalcemia does not weaken skeletal muscle contractions because sufficient calcium is stored in skeletal muscle cells. Cardiac muscle cells, on the other hand, do not have large stores of calcium but rely instead on calcium from the blood for contraction.  Hyperparathyroidism may be caused by; – an adenoma, – hyperplasia, – secondary to renal failure. It causes: hypercalcemia, or high serum calcium levels leading to: – forceful cardiac contractions – osteoporosis, weakening the bone so that it fractures easily – increase predisposition to kidney stones  Calcium metabolism may be modified by other factors, such as the presence of vitamin D and serum phosphate levels. Serum levels of PTH and calcium may vary depending on the specific cause of the problem. Patients who are immobile or have bone cancer, have hypercalcemia with a low level of PTH In patients with severe renal disease, there is hypocalcemia due to: 1- Decreased activation of vitamin D in the kidneys, vitamin D is essential for calcium absorption and metabolism. 2- Renal failure also leads to retention of phosphate ion and hyperphosphatemia. Because calcium and phosphate have a reciprocal relationship, hypocalcemia results. In this case, hypocalcemia leads to high levels of PTH.  Therefore, any changes in the bone, kidneys, or digestive tract are significant in determining the cause of calcium imbalance, as are serum levels of calcium, phosphate, and PTH. Hypoparathyroidism Hyperparathyroidism Common effects of parathyroid hormone imbalances  Treatment Depends on the cause. – Any underlying disorder should be treated. Chronic hypoparathyroidism may be treated with calcium and vitamin D. Parathyroidectomy may be required for hyperparathyroidism