Metabolism and Endocrine System Disorders (NCM 116 GEP) PDF

DISORDERSOF THE ENDOCRINESYSTEM NCM 116 METABOLISM 1 ANATOMYAND PHYSIOLOGY Endocrine System: Duct-less glands growth and development metabolism of energy muscle and adipose tissue distribution sexual development fluid and electrolyte balance inflammation and...

DISORDERSOF THE ENDOCRINESYSTEM NCM 116 METABOLISM 1 ANATOMYAND PHYSIOLOGY Endocrine System: Duct-less glands growth and development metabolism of energy muscle and adipose tissue distribution sexual development fluid and electrolyte balance inflammation and immune responses 2 ENDOCRINEGLANDSAND HORMONES 3 STIMULUSOFHORMONERELEASE Hormones: released into the blood Control of Hormone Release: 1. Hormonal stimulus – activated by other hormones 2. Humoral stimulus – activated by changing blood levels of certain ions and nutrients 3. Neural stimulus – activated by nerve fibers 4 STIMULUSOFHORMONERELEASE 5 HOMEOSTASIS Feedback Mechanisms: controls and stabilizes body balance 1.Negative Feedback - results when a change in condition triggers action that reverses the change 2.Positive Feedback - results in having the body react to a change by amplifying it FEEDBACKMECHANISMS DISORDERSOFTHE PITUITARYGLAND NCM 116 METABOLISM ANATOMYAND PHYSIOLOGY Pituitary Gland: Anterior and Posterior Lobe Hypophysis “Master gland” - controls other glands through its secretions Controlled by hypothalamic hormones 9 HYPOTHALAMICPITUITARYAXIS 1 0 ANTERIOR PITUITARYGLAND Adenohypophysis: Glandular component Hormones: Somatotropin – Growth Hormone Prolactin Thyroid Stimulating Hormone (TSH) Adrenocorticotropic Hormone (ACTH) Gonadotropic Hormones – Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Melanocyte Stimulating Hormone (MSH) 1 1 ANTERIOR PITUITARYGLAND 1 2 ANTERIORPITUITARYGLANDDISORDERS Hyperfunction and Hypofunction 1.Hyperpituitarism Growth Hormone Excess 2. Hypopituitarism Growth Hormone Deficiency 1 3 HYPERPITUITARISM Over secretion of the anterior pituitary gland most commonly involves ACTH and GH and results in Cushing’s Syndrome of Acromegaly Etiology: Anterior pituitary gland adenomas, anterior pituitary gland hyperplasia and carcinoma 1 4 ANTERIORPITUITARYGLANDDISORDERS 1 5 HYPERPITUITARISM Clinical Manifestations: Amenorrhea Paresthesia Galactorrhea Headache Infertility Nausea and Vomiting Impotence and loss of libido Seizures Blurred vision or Double vision 1 6 GROWTH HORMONEEXCESS Etiology: Pituitary adenomas (tumors) and damage secondary to trauma Growth Hormone Excess in Children Gigantism: GH excess before puberty or closure of the epiphyses of the long bones 1 7 GROWTHHORMONEEXCESS:GIGANTISM 1 8 GROWTH HORMONEEXCESS Etiology: Pituitary adenomas (tumors) and damage secondary to trauma Growth Hormone Excess in Adults Acromegaly: GH excess after puberty or closure of the epiphyses of the long bones. 1 9 GROWTH HORMONE EXCESS:ACROMEGALY Clinical Manifestations: Enlarged bones of the hands and feet Enlarged membranous bones of the face and skull Enlarged cartilaginous structures in the larynx and respiratory tract Kyphosis due to vertebral changes lead to Arthralgia, degenerative arthritis of the spine, hips and knees Cardiomegaly and accelerated atherosclerosis 2 0 GROWTH HORMONE EXCESS:ACROMEGALY 2 1 HYPOPITUITARISM Under secretion of the anterior pituitary gland commonly involves all of its hormones. Etiology: destruction of the anterior pituitary lobe, diseases of the pituitary gland itself or the hypothalamus, radiation therapy to the head and neck area and space occupying lesions 2 2 HYPOPITUITARISM Clinical Manifestations: Decreased growth in children Cold intolerance Impairment of GH secretion Dry skin Amenorrhea Mental dullness Decreased libido Weakness Erectile dysfunction Nausea Hypogonadism Anorexia 2 3 GROWTH HORMONEDEFICIENCY Etiology: Pituitary adenomas (tumors) and damage secondary to trauma Congenital Growth Hormone Deficiency – associated with decreased birth length, decrease in growth rate. Growth Hormone Deficiency in Children – normal intelligence, short stature (dwarfism), obesity with immature facial features, and some delay in skeletal maturation. Puberty is often delayed. 2 4 GROWTHHORMONEDEFICIENCY:DWARFISM 2 5 GROWTH HORMONEDEFICIENCY Etiology: Pituitary adenomas (tumors) and damage secondary to trauma Growth Hormone Deficiency in Adults – decrease in lean body mass, increase in fat mass, hyperlipidemia, decreased bone mineral density and reduced exercise capacity. 2 6 GROWTH HORMONEDEFICIENCY 2 7 ANTERIORPITUITARYGLANDDISORDERS Diagnostics: Assessment of visual acuity and visual fields CT scans and MRI are used to diagnose the presence and extent of pituitary tumors. Serum levels of pituitary hormones may be obtained along with measurements of hormones of target organs (thyroid, adrenals) to assist in diagnosis. 2 8 ANTERIORPITUITARYGLANDDISORDERS Management: Hypophysectomy surgical removal of the pituitary tumor through a transsphenoidal approach is the usual treatment. 2 9 HYPOPHYSECTOMY 3 0 POSTERIORPITUITARYGLAND Neurohypophysis: Neural component Hormones: Vasopressin or Antidiuretic Hormone (ADH) Oxytocin 3 1 POSTERIORPITUITARYGLANDDISORDERS Diabetes Insipidus (DI) – a disorder characterized by a deficiency in ADH(Vasopressin). Etiology: A. Neurogenic or Central DI: head trauma, brain tumor, or surgical ablation or irradiation of the pituitary gland, infections of the CNS (meningitis, encephalitis, tuberculosis) 3 2 POSTERIORPITUITARYGLANDDISORDERS Diabetes Insipidus (DI) – a disorder characterized by a deficiency in ADH(Vasopressin). Etiology: B. Nephrogenic DI: genetic or acquitted failure of the renal tubules to respond to ADH. Acquired nephrogenic DI is related to disorders and drugs that damage the renal tubules. 3 3 DIABETESINSIPIDUS Clinical Manifestations: Polydipsia – excessive thirst Polyuria – large volumes of dilute urine Nocturia – excessive night time urination DI cannot be controlled by limiting fluid intake, because high-volume loss of urine continues even without fluid replacement 3 4 DIABETESINSIPIDUS 3 5 DIABETESINSIPIDUS Diagnostics: Fluid deprivation test is carried out by withholding fluids for 8 to 12 hours or until 3% to 5% of the body weight is lost. Measurement of plasma levels of ADH and plasma and urine osmolality. 3 6 DIABETESINSIPIDUS Management: Replacement of ADH with synthetic vasopressin (Desmopressin) Considerations: used cautiously in patients with coronary artery disease Ensure adequate fluid replacement Identify the correct underlying intracranial pathology 3 7 POSTERIORPITUITARYGLANDDISORDERS Syndrome of Inappropriate Antidiuretic Hormone (SIADH) excessive secretion of ADH from the pituitary gland Etiology: Disorders of the CNS such as head injury, brain surgery or tumor, and infection, are thought to produce SIADH by direct stimulation of the pituitary gland. 3 8 SYNDROMEOFINAPPROPRIATEADH Clinical Manifestations: Inability to excrete a dilute urine Weight gain secondary to fluid retention Dilutional Hyponatremia Diagnostics: Serum sodium Serum and urine osmolality 3 9 SYNDROMEOFINAPPROPRIATEADH 4 0 SYNDROMEOFINAPPROPRIATEADH Management: Elimination of the underlying cause Restricting fluid intake Diuretics such as furosemide may be used along with fluid restriction if severe hyponatremia is present 4 1 SYNDROMEOFINAPPROPRIATEADH Management: Close monitoring of fluid intake and output, daily weight, urine and blood chemistries, and neurologic status Hypertonic saline for emergency correction of hyponatremia in severe SIADH 4 2 DISORDERSOFTHE THYROIDGLAND NCM 116 METABOLISM ANATOMYAND PHYSIOLOGY Thyroid Gland The thyroid gland is a butterfly shaped organ located in the lower neck, anterior to the trachea. It consists of two lateral lobes connected by an isthmus. 4 4 THYROIDGLAND Thyroid Hormones 1. Thyroxine (T4) – contains 4 iodine atoms in each molecule 2. Triiodothyronine (T3) – contains 3 iodine atoms in each molecule 3.Calcitonin – Thyrocalcitonin – secreted in response to high plasma levels of calcium and it reduces the plasma level of calcium by increasing its deposition in the bones. 4 5 HYPOTHALAMICPITUITARYTHYROIDAXIS Thyroid Hormones control cellular metabolic activity accelerate metabolic processes enhance cell replication for growth 4 6 THYROIDHORMONES 4 7 THYROIDGLANDDISORDERS Hypofunction of the Thyroid Gland Cretinism or Congenital hypothyroidism - Inadequate secretion of thyroid hormone during fetal and neonatal development 4 8 THYROIDGLANDDISORDERS Hypofunction of the Thyroid Gland Goiter commonly occurs with iodine deficiency resulting in low level of thyroid hormones causing increased TSH levels. Elevated TSH leads to overproduction of thyroid hormones and hypertrophy of the thyroid gland. 4 9 THYROIDGLANDDISORDERS Hypofunction of the Thyroid Gland Hypothyroidism results from suboptimal levels of thyroid hormone with increased secretion of TSH and TRH Etiology: Autoimmune thyroiditis (Hashimoto’s Disease where the immune system attacks the thyroid gland. Atrophy of the thyroid gland with aging, therapy for hyperthyroidism, iodine deficiency and iodine excess, pituitary tumors and other traumatic brain injury 5 0 HYPOTHYROIDISM Hypofunction of the Thyroid Gland Hypothyroidism Myxedema – advanced form of Hypothyroidism implies the presence of nonpitting mucous type edema caused by an accumulation of hydrophilic mucopolysaccharide substance in connective tissues throughout the body. 5 1 MYXEDEMA 5 2 HYPOTHYROIDISM Clinical Manifestations: Extreme fatigue Generalized slowing of body functions Hair loss Cold intolerance - Subnormal body Brittle nails temperature Dry skin Elevated serum cholesterol levels Amenorrhea Puffy face and periorbital edema Loss of libido Decreased gastrointestinal motility Lethargy Impairment of muscle function Weight gain Pericardial or Pleural effusion may Slow mentation develop 5 3 HYPOTHYROIDISM 5 4 HYPOTHYROIDISM Myxedema Coma Decompensated state of severe hypothyroidism in which the patient is hypothermic and unconscious. The patient may initially show signs of depression, somnolence, lethargy and diminished cognitive status. 5 5 HYPOTHYROIDISM Management: Synthetic thyroid hormone – levothyroxine (Synthroid or Levothroid) Prevention of cardiac dysfunction and monitoring of angina, ischemia and infarction. Prevention of medication interaction: Thyroid hormones may increase blood glucose levels and increase the pharmacologic effects of other drugs. 5 6 THYROIDGLANDDISORDERS Hyperfunction of the Thyroid Gland Hyperthyroidism Over secretion of thyroid hormones is manifested by a greatly increased metabolic rate. Etiology: hyperactivity of the thyroid gland, multinodular goiter, adenoma of the thyroid and thyroiditis, excessive intake of thyroid hormone, and Grave’s Disease – autoimmune disorder bringing abnormal stimulation of the thyroid gland 5 7 HYPERTHYROIDISM Clinical Manifestations: Thyrotoxicosis group of signs and symptoms with well-developed hyperthyroidism Nervousness and apprehensive Palpitations with abnormally rapid pulse Heat intolerance Shortness of breath Flushed, warm and moist skin – excessive sweating Exophthalmos (bulging eyes) 5 8 HYPERTHYROIDISM Clinical Manifestations: Pretibial myxedema Muscle cramps Increased appetite Amenorrhea Progressive weight loss Diarrhea Fatigability and weakness Elevated blood pressure Tremors Cardiac dysrhythmias 5 9 HYPERTHYROIDISM 6 0 HYPERTHYROIDISM 6 1 HYPERTHYROIDISM Thyroid Storm It is an acutely exaggerated manifestation of the thyrotoxic state. Thyroid storm is manifested by a very high fever, extreme cardiovascular effects (angina, congestive failure, tachycardia), and severe CNS effects (agitation, restlessness, delirium). 6 2 HYPERTHYROIDISM Management: Radioactive Iodine Therapy – destroys the overactive thyroid cells. Observe for signs of thyroid storm. This therapy is contraindicated in pregnancy and breastfeeding to prevent fetal hypothyroidism. 6 3 HYPERTHYROIDISM Management: Antithyroid medications - inhibit one or more stages in thyroid hormone synthesis or hormone release, block the utilization of iodine, reduce the amount of thyroid tissue resulting to decreased thyroid hormone production. propylthiouracil (PTU) or methimazole (Tapazole) blocks the conversion of T4 to T3. Watch out for signs of agranulocytosis and thrombocytopenia. 6 4 HYPERTHYROIDISM Management: Thyroidectomy Surgical removal of the thyroid gland 6 5 THYROIDGLANDDISORDERS Diagnostics: Serum TSH Serum Free T4 Serum T3 and T4 Fine Needle Aspiration Biopsy Thyroid Scan 6 6 THYROIDGLANDDISORDERS Diagnostics: Radioactive Iodine Uptake – measures the rate of iodine uptake by the thyroid gland. The patient is administered a tracer dose of iodine and a count over the thyroid gland, detecting the gamma rays released from the breakdown of iodine. 6 7 RADIOACTIVEIODINEUPTAKE 6 8 DISORDERSOF THE PARATHYROIDGLAND NCM 116 METABOLISM ANATOMYAND PHYSIOLOGY Parathyroid Gland The parathyroid glands are 4 structures situated in the neck and embedded in the posterior aspect of the thyroid gland. 7 0 PARATHYROIDGLAND Parathormone hormone that regulates calcium and phosphorus metabolism increases calcium absorption from the kidney, intestines and bones raising the blood calcium levels reduces the reabsorption of phosphate from the proximal tubule of the kidney lowering blood phosphorus level through the urine 7 1 PARATHORMONE 7 2 PARATHYROID GLANDDISORDERS Hyperfunction of the Parathyroid Gland Hyperparathyroidism caused by overproduction of parathormone characterized by bone decalcification and the development of renal calculi containing calcium and hypercalcemia Etiology: parathyroid adenomas, parathyroid hyperplasia, parathyroid carcinoma, compensatory response to chronic hypocalcemia, vitamin D deficiency, decreased renal activation of vitamin D (renal failure) 7 3 HYPERPARATHYROIDISM Clinical Manifestations: Hypercalcemia Hypercalciuria due to increased renal filtration load of calcium Hypophosphatemia Hyperphosphaturia Renal Calculi / Kidney stones 7 4 HYPERPARATHYROIDISM Clinical Manifestations: Pathologic fractures, deformities, kyphosis, compressional fractures of the vertebrae Fatigue, muscle weakness Hypertension and cardiac dysrhythmias Psychological effects like psychosis are caused by the direct action of calcium on the brain and nervous system 7 5 HYPERPARATHYROIDISM 7 6 HYPERPARATHYROIDISM Diagnostics: Serum parathormone radioimmunoassay Serum calcium levels Bone scans and x-rays Parathyroid ultrasound, MRI Fine Needle Aspiration Biopsy 7 7 HYPERPARATHYROIDISM Management: Parathyroidectomy – recommended treatment Watch out for signs of hypocalcemia or tetany post parathyroidectomy Hydration therapy with restricted calcium diet Monitor manifestations of renal calculi like abdominal pain and hematuria. 7 8 HYPERPARATHYROIDISM Management: Mobility is encouraged. Bisphosphonates - treats hypercalcemia by inhibiting osteoclastic bone resorption e.g. alendronate (Fosamax) Calcitonin and corticosteroids combination administration is given to Hypercalcemic crisis (extreme elevation of serum calcium resulting in neurologic and cardiovascular emergencies) to reduce the serum calcium levels by increasing calcium deposition in bone. 7 9 PARATHYROIDECTOMY 8 0 PARATHYROID GLANDDISORDERS Hypofunction of the Parathyroid Gland Hypoparathyroidism characterized by inadequate parathormone secretion Deficiency of PTH results in increased blood phosphate and decreased blood calcium levels. Etiology: damage to parathyroid glands during parathyroidectomy, thyroidectomy or radical neck dissection 8 1 HYPOPARATHYROIDISM Clinical Manifestations: Hypocalcemia Compensatory hypocalciuria due to low serum calcium Hyperphosphatemia Hypophosphaturia 8 2 HYPOPARATHYROIDISM Clinical Manifestations: Tetany secondary to hypocalcemia: numbness, tingling and cramps in the extremities, bronchospasm, laryngeal spasm and carpopedal spasm Cardiac dysrhythmias Seizures and delirium 8 3 HYPOPARATHYROIDISM Diagnostics: Positive Trousseau’s sign suggestive of latent tetany Positive Chvostek’s sign suggestive of latent tetany Serum calcium levels Serum phosphate levels Increased bone density in x-rays and bone scans 8 4 TETANY 8 5 HYPOPARATHYROIDISM Management: Monitoring for early signs of tetany and hypocalcemia in post- operative patients of thyroidectomy, parathyroidectomy or radical neck dissection IV calcium gluconate – must be kept at bedside for immediate treatment of hypocalcemia and tetany post thyroidectomy to increase serum calcium levels Parenteral parathormone – treatment of acute hypoparathyroidism with tetany. Monitor closely for allergic reactions and changes in serum calcium levels. 8 6 HYPOPARATHYROIDISM Management: Provide an environment free from noise, bright lights or sudden movement because of neuromuscular irritability. Prepare for emergency tracheostomy, mechanical ventilation and bronchodilating agents for respiratory distress. Low phosphorus and high calcium diet. High vitamin D diet to enhance calcium absorption from the GIT. 8 7 DISORDERSOFTHE ADRENALGLAND NCM 116 METABOLISM ANATOMYAND PHYSIOLOGY Adrenal Gland These glands are a pair of organs attached to the upper portion of each kidney. Each adrenal gland is two glands with separate independent functions. Parts: Adrenal Medulla – inner portion: SNS (neural control) - catecholamines Adrenal Cortex – outer portion: HPA axis (hormonal control) - glucocorticoids, mineralocorticoids, androgens 8 9 SNS& HYPOTHALAMICPITUITARYADRENALAXIS 9 0 ADRENALMEDULLA Catecholamines: Epinephrine and Norepinephrine stimulate the fight or flight response regulate metabolic pathways to promote catabolism and stored fuels to meet caloric needs from endogenous sources. decrease blood flow to tissues that are not needed in emergency situations such as the GIT increase blood flow to tissues that are important for effective fight or flight such as cardiac and skeletal muscle elevate the blood glucose levels and the basal metabolic rate. 9 1 CATECHOLAMINES 9 2 ADRENALCORTEX Glucocorticoids: Cortisol influence metabolism on all organs especially on glucose metabolism: increasing blood glucose levels inhibit the inflammatory response to tissue injury and to suppress allergic manifestations cortisol or hydrocortisone indirectly constrict blood vessels slowing blood loss and prevents inflammation after an injury cortisol indirectly acts on bone by blocking calcium absorption which decreases bone cell growth 9 3 ADRENALCORTEX Mineralocorticoids: Aldosterone aldosterone functions for electrolyte metabolism (blood volume and salt balance) increasing sodium ions reabsorption at the renal tubules and GI epithelium in exchange for potassium or hydrogen ions excretion conserves water and increases blood pressure (important in compensating for fluid loss from severe bleeding) 9 4 GLUCOCORTICOIDS & MINERALOCORTICOIDS 9 5 ADRENALCORTEX Androgens: steroid hormones that exert effects similar to those of the male sex hormones The adrenal gland may also secrete small amounts of some estrogens, or female sex hormones. 9 6 ADRENALGLANDDISORDERS Hyperfunction of the Adrenal Gland Pheochromocytoma a tumor that is usually benign and originates from the chromaffin cells (neuroendocrine cells) of the adrenal medulla. Pheochromocytoma causes a sympathetic nervous system overactivity due to increased catecholamine secretion. Etiology: mutated genetic inheritance 9 7 PHEOCHROMOCYTOMA Clinical Manifestations: Hypertension Tachycardia Headache Flushing Diaphoresis Tremors Palpitations Hyperglycemia 9 8 PHEOCHROMOCYTOMA 9 9 PHEOCHROMOCYTOMA Diagnostics: Urine and plasma levels of catecholamines and metanephrine (MN), a catecholamine metabolite, are the most direct and conclusive tests Total plasma catecholamine concentration is measured with the patient supine and at rest for 30 minutes free from stress. clonidine (Catapres) suppression test may be performed if plasma and urine catecholamine results are inconclusive. Imaging studies: CT, MRI andultrasound 10 0 PHEOCHROMOCYTOMA Management: Bedrest with of bed elevated promoting orthostatic decrease in blood pressure Close monitoring with ECG changes and careful administration of anti-hypertensives. Adrenalectomy – surgical removal of the tumor as the definitive treatment. Hypotension and hypoglycemia may occur in the post-operative period because of the sudden withdrawal of excessive amount of catecholamines. 10 1 ADRENALECTOMY Adrenalectomy Manipulation of the tumor during surgical excision may cause release stored epinephrine and norepinephrine with marked increases in blood pressure and changes in the heart rate. 10 2 ADRENALGLANDDISORDERS Hyperfunction of the Adrenal Gland Cushing’s Syndrome results from excessive adrenocortical activity symptoms are a result of over secretion of glucocorticoids and androgens, mineralocorticoid secretion may also be affected. Etiology: excessive use of corticosteroid medications, hyperplasia of the adrenal cortex, tumor of the pituitary gland, ectopic and non-pituitary ACTH secreting tumor 10 3 CUSHING’SSYNDROME Clinical Manifestations: Glucose intolerance and insulin resistance Hyperglycemia Immunosuppression Weight gain Truncal Obesity: heavy trunk with thin extremities Buffalo hump and Moon face Arrest of growth Musculoskeletal changes: osteoporosis, kyphosisand compression fractures 10 4 CUSHING’SSYNDROME Clinical Manifestations: Muscle wasting due to increased catabolism of proteins Thin fragile skin with ecchymoses and striae Weakness Hypertension or Heart failure Virilization – appearance of masculine traits and the recession of feminine traits: hirsutism, atrophy of breasts, menses cease, clitoris enlarges, voice deepens and loss of libido Mood changes and psychosis may occur Gastric ulceration and bleeding 10 5 CUSHING’SSYNDROME 10 6 CUSHING’SSYNDROME Diagnostics: Dexamethasone suppression test – widely used and most sensitive Serum sodium levels (increased) and serum potassium levels (decreased) Serum glucose levels Serum and 24-hour urine cortisol levels Serum radioimmunoassay of ACTH CT, MRI or ultrasound to localize adrenal tumors 10 7 CUSHING’SSYNDROME Management: Surgical removal of the pituitary tumor: transsphenoidal hypophysectomy Radiation of the pituitary gland Adrenalectomy – treatment of choice in patients with primary hypertrophy Temporary replacement therapy with hydrocortisone post operatively 10 8 ADRENALGLANDDISORDERS Hypofunction of the Adrenal Gland Addison’s Disease Adrenocortical insufficiency occurs when adrenal cortex function is inadequate to meet the patient’s need for cortical hormones. Etiology: Autoimmune or idiopathic atrophy, infection, surgical removal of the adrenal glands, corticosteroid use and rapid withdrawal resulting to adrenal cortical atrophy, pituitary gland hyposecretion 10 9 ADDISON’SDISEASE Clinical Manifestations: Hypoglycemia Emaciation GI symptoms and anorexia Hyponatremia Muscle weakness Hyperkalemia Fatigue Confusion and restlessness 11 0 ADDISON’SDISEASE Clinical Manifestations: Dark pigmentation of the mucous membranes and the skin of the knuckles, elbows and knees Decreased cardiac output and Hypotension Addisonian Crisis – develops with disease progression and acute hypotension manifested by circulatory shock, cyanosis, pallor, apprehension, rapid and weak pulse, rapid respirations and low blood pressure Sparse axillary and pubic hair in women 11 1 ADDISON’SDISEASE 11 2 ADDISON’SDISEASE Diagnostics: Serum cortisol Plasma ACTH Serum glucose levels Serum sodium levels(decreased) and serum potassium levels (increased) 11 3 ADDISON’SDISEASE Management: Administering fluids and restoring blood circulation Corticosteroid administration with hydrocortisone Antibiotics if condition is precipitated by an infection in the adrenals Possible lifelong replacement of corticosteroids and mineralocorticoids to prevent recurrence of adrenal insufficiency IV administration of fluids, glucose and electrolytes 11 4 DISORDERSOF THE ENDOCRINEPANCREAS NCM 116 METABOLISM ANATOMYAND PHYSIOLOGY Pancreas: exocrine functions: secretion of pancreatic enzymes into the gastrointestinal (GI) tract through the pancreatic duct endocrine functions: secretion of insulin, glucagon, and somatostatin directly into the bloodstream The pancreas relies on humoral control and is also influenced by neural factors for enzymatic and hormonal secretion. 11 6 ENDOCRINEPANCREAS Islets of Langerhans: Collection of cells embedded in the pancreatic tissue alpha cells - secrete glucagon beta cells - secrete insulin delta cells - secrete somatostatin 11 7 ENDOCRINEPANCREAS Hormones: Insulin Lowers blood glucose levels Stimulates glycogenesis Transports and metabolizes glucose for energy Inhibits glycogenolysis and gluconeogenesis Enhances storage of dietary fat in adipose tissue Accelerates transport of amino acids (derived from dietary protein) into cells 11 8 ENDOCRINEPANCREAS Hormones: Glucagon Raises blood glucose levels Stimulates glycogenolysis Somatostatin Growth Hormone Inhibiting Hormone (GHIH) Lowers blood glucose levels by inhibiting growth hormone and glucagon release 11 9 NUTRIENTMETABOLISMAND STORAGE Carbohydrates: Glucose – quick source of energy and fuel needed for vital functions Glycogen – stored form of glucose in the liver Glycogenesis – conversion of extra glucose into glycogen in the liver Glycogenolysis – conversion of glycogen back to glucose in the liver during hypoglycemia 12 0 NUTRIENTMETABOLISMAND STORAGE Fats: most efficient form of fuel storage. When there is a high saturation of glycogen, the excess glucose is converted into fatty acids stored as triglycerides. Proteins: are essential for the formation of all body structures, including genes, enzymes, muscle, bone matrix and the blood. Amino acids are the building blocks of proteins. 12 1 NUTRIENTMETABOLISMAND STORAGE Fats and Proteins: Gluconeogenesis It is the generation of glucose from non-carbohydrate carbon substrates such as fatty acids, and amino acids in the liver especially during hypoglycemia. 12 2 NUTRIENTMETABOLISMAND STORAGE 12 3 ENDOCRINE PANCREASDISORDERS Diabetes Mellitus a group of metabolic diseases characterized by increased levels of glucose in the blood (hyperglycemia) resulting from defects in insulin action and secretion Risk Factors: Family history of Diabetes Obesity Age 45 years old and above Hypertension History of gestational Diabetes High HDL cholesterol levels and triglyceride levels 12 4 DIABETESMELLITUS Insulin Dependent Diabetes Mellitus (IDDM) Type 1 Diabetes Mellitus acute onset usually before 30 years of age Etiology: destruction of pancreatic beta cells due to combined genetic, immunologic, and possibly environmental factors (viral) 12 5 DIABETESMELLITUS Non-insulin Dependent Diabetes Mellitus (NIDDM) Type 2 Diabetes Mellitus occurs more commonly among people who are older than 30 years of age and obese Etiology: insulin resistance and impaired insulin secretion due to genetic factors 12 6 DIABETESMELLITUS Gestational Diabetes Mellitus (GDM) any degree of glucose intolerance with its onset during pregnancy occurs in as many as 14% of pregnant women and increases their risk for hypertensive disorders during pregnancy Etiology: secretion of placental hormones leading to insulin resistance 12 7 DIABETESMELLITUS 12 8 DIABETESMELLITUS Clinical Manifestations: Hyperglycemia Glycosuria Osmotic Diuresis Polyuria – increased urination Polydipsia – increased thirst Polyphagia – increased appetite Fatigue and weakness 12 9 DIABETESMELLITUS Clinical Manifestations: Ketonuria Vision changes Tingling or numbness in hands and feet Slow healing wounds andlesions Recurrent infections Weight loss 13 0 DIABETESMELLITUS 13 1 DIABETESMELLITUS Diagnostics: Fasting Blood Sugar Random Blood Sugar Postprandial Sugar HgbA1C / Hemoglobin A1C (Glycohemoglobin/ Glycated hemoglobin/ Glycosylated Hemoglobin) A1C is a blood test that reflects average blood glucose levels over a period of approximately 2 to 3 months. 13 2 DIABETESMELLITUS Diagnostics: Oral Glucose Tolerance Test (OGTT) A glucose load solution is given orally after fasting and the plasma glucose response will be measured at selected intervals of 2 hours. Urine glucose and ketone levels – urine dipstick Urine test for albumin Serum cholesterol and triglyceride levels 13 3 DIABETESMELLITUS 13 4 DIABETESMELLITUS Management: Goal: normalize insulin activity and blood glucose levels to reduce the development of vascular and neuropathic complications Nutritional Therapy Nutrition and meal planning and weight control Weight loss for obese patients Exercise increases the uptake of glucose by body muscles and improves insulin utilization 13 5 DIABETESMELLITUS Management: Monitoring Self-Monitoring of Blood Glucose (SMBG) enables people with Diabetes to adjust their treatment regimen and to obtain optimal blood glucose control 13 6 DIABETESMELLITUS Management: Monitoring Continuous Glucose Monitoring System (CGMS) uses a sensor attached to an infusion set inserted subcutaneously in the abdomen and connected to the device worn on abelt 13 7 DIABETESMELLITUS Management: Pharmacologic Therapy Insulin Basal Insulin – or background insulin is necessary to maintain blood glucose levels irrespective of meals Types of Insulin Rapid-acting Short-acting Intermediate-acting Long-acting 13 8 INSULINTHERAPY Rapid-acting Insulins - rapid onset and short duration - instruct patients to eat no more than 5 to 15 minutes after injection - used with intermediate-acting insulins Short-acting Insulins - regular insulin - clear solution -given 20 to 30 minutes before meals, either alone or in combination with intermediate-acting insulins - approved for IVuse 13 9 INSULINTHERAPY Intermediate-acting Insulins - appear white and cloudy -may function as basal insulins but split into 2 injections for 24-hour coverage - often combined with rapid or short acting insulins Long-acting Insulins - approved for use as basal insulin - absorbed very slowly for 24 hours and is given once daily - not mixed with other insulins for it may cause precipitation - lowers blood glucose when rapid-acting insulins stop working 14 0 INSULINTHERAPY ONSET (length of time before PEAK DURATION AGENT insulin reaches (time period when (how long insulin TYPE bloodstream) insulin is most effective) works for) Humalo 10 – 15 minutes 1 hour 2 – 4 hours g 5 – 15 minutes 40 – 50 minutes 2 – 4 hours Rapid-acting Novolog 5 – 15 minutes 30 – 60 minutes 2 hours Apidra Short-acting Humulin R 30 minutes – 1 hour 2 – 3 hours 4 – 6 hours Intermediate - acting Humulin N 2 – 4 hours 4 – 12 hours 16 – 20 hours Lantus Long-acting Levemir 1 hour Continuous (no peak) 24 hours 14 1 INSULINTHERAPY Complications: Local Allergic Reactions Systemic Allergic Reactions Insulin Lipodystrophy Lipoatrophy – loss of subcutaneous fat with dimpling or pitting Lipohypertrophy – development of fibrofatty masses at the injection site Resistance to Injected Insulin Morning Hyperglycemia 14 2 INSULINTHERAPY Complications: Morning Hyperglycemia – an elevated blood glucose level on arising in the morning caused by an insufficient level of insulin. Causes: Dawn Phenomenon – hyperglycemia at around 3 AM caused by surges of growth hormone secretion increasing the need of insulin Somogyi Effect – nocturnal hypoglycemia followed by rebound hyperglycemia Insulin Waning – the progressive increase in blood glucose from bedtime to morning 14 3 INSULINLIPODYSTROPHY 14 4 INSULINTHERAPY 14 5 INSULINTHERAPY 14 6 DIABETESMELLITUS Management: Pharmacologic Therapy Oral Antidiabetic Agents / Oral Hypoglycemic Agents used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin or synthetic insulin 14 7 ORALHYPOGLYCEMIC AGENTS Sulfonylureas – stimulate beta cells to secrete insulin; may improve binding between insulin and insulin receptors or increase the number of insulin receptors e.g. glipizide, glyburide, glimepiride Biguanides – inhibit production of glucose by the liver and increase the body tissues’ sensitivity to insulin e.g. metformin Alpha-Glucosidase Inhibitors – delay absorption of complex carbohydrates in the intestine and slow entry of glucose into systemic circulation e.g. acarbose, miglitol 14 8 ORALHYPOGLYCEMIC AGENTS Non-Sulfonylurea Insulin Secretagogues – stimulate pancreas to secrete insulin e.g. repaglinide, nateglinide Thiazolidinediones / Glitazones – sensitize body tissue to insulin; stimulate insulin receptor sites to lower blood glucose and improve insulin action e.g. pioglitazone, rosiglitazone Dipeptidyl Peptidase-4 (DPP-4) Inhibitor – increase and prolong the action of incretin, a hormone that increases insulin release and decreases glucagon levels, with the result of improved glucose control e.g. sitagliptin, vildagliptin 14 9 DIABETESMELLITUS Management: Education Diabetic patients must master the concepts and skills necessary for long-term management and avoidance of potential complications. Insulin treatment / replacement Blood sugar monitoring Monitoring for side effects of treatment Monitoring for complications of Diabetes Mellitus 15 0 DIABETESMELLITUS Complications: Hypoglycemia occurs when the blood glucose falls to less than 50 to 60 mg/dLbecause of too much insulin or oral hypoglycemic agents, too little food, or excessive physical activity Diagnostics: Serum glucose testing 15 1 HYPOGLYCEMIA Clinical Manifestations: Sweating Impaired coordination Tremors Double vision Tachycardia and Palpitations Drowsiness Nervousness Disoriented behavior Hunger Seizures Lightheadedness Difficulty arousing from sleep Confusion and memory lapses Loss of consciousness 15 2 HYPOGLYCEMIA Management: 15 g of fast acting Carbohydrates: 4 – 6 oz of fruit juice or soda 6 – 10 hard candies 2 – 3 teaspoons of sugar or honey Glucagon 1 mg IM or subcutaneous 25 – 50 mL of D50W (50% dextrose in water) – IV 15 3 DIABETESMELLITUS Complications: Diabetic Ketoacidosis (DKA) -caused by increased fat breakdown in response to energy needs in the absence of proper glucose utilization due to inadequate amount of insulin -fat breakdown results in an increased production of ketone bodies as byproduct causing acidosis - this condition usually affects Type I DM 15 4 DIABETICKETOACIDOSIS Diagnostics: Serum glucose testing Serum bicarbonate – low Serum pH – low (6.8 to 7.3 - acidic) Blood and urine ketone test ABG – low partial pressure of carbon dioxide (PCO2) Serum sodium and potassium Serum creatinine, BUN and hematocrit (CBC) 15 5 DIABETICKETOACIDOSIS Clinical Manifestations: Hyperglycemia Polydipsia Blurred vision Weakness Headache Orthostatic hypotension Dehydration and electrolyte loss due to polyuria 15 6 DIABETICKETOACIDOSIS Clinical Manifestations: Acidosis Abdominal pain Nausea and vomiting Hyperventilation – Kussmaul respirations Fruity breath odor (acetone breath) Loss of consciousness 15 7 DIABETICKETOACIDOSIS Management: Insulin treatment Fluid and electrolyte replacement Reversing acidosis through insulin treatment 15 8 DIABETESMELLITUS Complications: Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS) -a severe condition of hyperosmolarity and hyperglycemia with alterations of the sensorium precipitated by an acute illness -ketosis and acidosis do not occur in HHNS when compared to DKA due to the presence of minimum insulin to prevent fat breakdown - this condition usually affects Type II DM 15 9 HYPERGLYCEMICHYPEROSMOLARNONKETOTICSYNDROME Diagnostics: Serum glucose levels Electrolytes – Serum sodium Blood Urea Nitrogen Complete Blood Count 16 0 HYPERGLYCEMICHYPEROSMOLARNONKETOTICSYNDROME Clinical Manifestations: Hyperglycemia Glycosuria Polyuria Dehydration Hypernatremia and increased osmolarity Hypotension Alterations in sensorium 16 1 HYPERGLYCEMICHYPEROSMOLARNONKETOTICSYNDROME Management: Fluid replacement Correction of electrolyte imbalances Insulin treatment 16 2 DIABETESMELLITUS Long Term Complications: Macrovascular Complications Blood vessel walls thicken and become occluded by plaque that adheres to the vessel walls and eventually blood flow is blocked (atherosclerotic changes). Coronary artery disease –MI Cerebrovascular disease – CVA Peripheral vascular disease –DVT 16 3 DIABETESMELLITUS Long Term Complications: Microvascular Complications Increase in blood glucose levels thickens the basement membrane of the capillaries into several times its normal thickness decreasing blood supply. Diabetic Nephropathy Diabetic Neuropathy Diabetic Retinopathy Foot and Leg Problems 16 4 DIABETESMELLITUSLONGTERMCOMPLICATIONS 16 5