NURS 6501 Advanced Pathophysiology Module 4 Knowledge Check Assignment

SIADH is a group of symptoms that occurs when antidiuretic hormone (ADH, arginine vasopressin) is secreted in the absence of osmotic or physiologic stimuli. These stimuli include: Increased serum osmolality, decreased plasma volume, and hypotension. A decrease in plasma osmolality normally inhibits ADH production and secretion. SIADH is characterized by fluid retention, dilutional hyponatremia, hypochloremia, concentrated urine, and lack of intravascular volume depletion. SIADH is characterized by normal to increased blood volume in normoproteinemia, nonedematous, and hyponatremic patients with normal renal and endocrine function. ADH regulates the body’s water balance. It is synthesized in the hypothalamus and stored in the posterior pituitary gland. When released into the circulation, it acts on the kidney’s distal tubules and collecting ducts, increasing their permeability to water. This decreases urine volume because more water is being reabsorbed and returned to the circulation. It also serves to produce more concentrated urine.

An adrenal insufficiency requires some type of trigger or stressor such as surgery, trauma, infection or acute withdrawal of glucocorticoids. The patient had several factors contributing to her present situation. She had RA x 20 years that necessitated oral prednisone. Increased levels of both glucocorticoids (primarily cortisol) and mineralocorticoids (primarily aldosterone) are needed for the body to adapt to the stress Corticotropin-releasing hormone (CRH) from the hypothalamus eventually prompts release of ACTH from the anterior pituitary gland. ACTH then stimulates release and 3 synthesis of cortisol from the adrenal cortex. Cortisol mobilizes amino acids from skeletal muscle and generally enhances the liver’s capacity for gluconeogenesis as well as enhances normal immune activity and maintenance of cardiovascular integrity. It also influences fat, carbohydrate and protein. Catecholamines cause vasoconstriction, which in the kidney, probably initiates release of renin, stimulating the rennin-angiotensionaldosterone-system (RAAS). Antidiuretic hormone (ADH, also called vasopressin), is released from the hypothalamus and posterior pituitary during periods of stress. Both aldosterone and ADH attempt to conserve water and electrolytes to sustain a sufficient vascular volume.

Primary hyperparathyroidism is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium balance. PTH secretion is increased and is not under the usual feedback control mechanisms. The Ca++ level in the blood increase because of increased resorption and GI absorption of calcium but fails to inhibit PTH secretion at normal levels of calcium because the feedback threshold for calcium is set at a higher level in the abnormal parathyroid tissues. Hypercalcemia and hypophosphatemia are the clinical hallmarks of hyperparathyroidism.

Increased renal filtration load of calcium leads to hypercalciuria. Hypercalcemia also affects proximal renal tubular functions, causing metabolic acidosis and production of abnormally alkaline urine. PTH hypersecretion enhances real phosphate excretion and results in hypophosphatemia and hyperphosphatemia. The combination of hypercalciuria, alkaline urine, and hyperphosphaturia leads to the formation of renal stones

Excessive osteoclastic and osteocytic activity results in increased bone reabsorption that weakens the bone. Kyphosis of the dorsal spine and compression fractures of the vertebral bodies are also seen in patients with hyperparathyroidism.

Hypoparathyroidism occurs when there is destruction of the parathyroid glands (autoimmune, surgical), abnormal parathyroid gland development, altered regulation of PTH production, or impaired PTH action. The acute manifestations of hypoparathyroidism (postsurgical hypoparathyroidism) are due to acute hypocalcemia.  The hallmark of acute hypocalcemia is tetany, which is a disorder of neuromuscular irritability. The symptoms of tetany may be mild (perioral numbness, paresthesia of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures, which must be distinguished from the generalized tonic muscle contractions that occur in severe tetany). The classic physical findings in patients with neuromuscular irritability due to latent tetany are Trousseau’s and Chvostek’s signs.

Because elevated blood glucose levels, water is osmotically attracted from body cells which results in intracellular dehydration and hypothalamic stimulation of thirst.

Hyperglycemia acts as an osmotic diuretic. The amount of glucose filtered by the glomeruli of the kidneys exceeds the amount that can be reabsorbed by the renal tubules. Glycosuria results accompanied by large amounts of water lost in the urine.

Depletion of cellular stores of carbohydrates, fats, and proteins results in cellular starvation and a corresponding increase in hunger.

Weight loss occurs because of fluid loss in osmotic diuresis and the loss of body tissue as fat and proteins are used for energy as a result of the effects of insulin deficiency.

Metabolic change result in poor use of food products, contributing to lethargy and fatigue. Sleep loss from severe nocturia also contributes to fatigue.

Islet cell autoantibodies (ICAs) were detected in serum from patients with autoimmune polyendocrine deficiency. They have subsequently been identified in 85 percent of patients with newly diagnosed type 1 diabetes and in prediabetic people.

Autoantigens form on insulin producing beta cells and circulate in the blood and lymphatics. This leads to processing and presentation of autoantigen by antigen presenting cells

There is activation of T helper 1 lymphocytes and T helper 2 lymphocytes There is activation of macrophages that release IL-1 and TNFα and activation of autoantigen specific T cytotoxic CD8 cells.

There is activation of B lymphocytes to produce islet cell autoantibodies and antiGAD65 antibodies. This cascade results in destruction of beta cells with decreased insulin production.

The most important concept is that DKA is caused by insulin deficiency and an increase in counterregulatory hormones that include glucagon, catecholamines, cortisol, and growth hormone. These counter regulatory hormones normally antagonize insulin buy increasing glucose production and decreasing tissue use of glucose. Insulin deficiency results in decreased glucose uptake, increased fat mobilization with release of fatty acids and accelerated gluconeogenesis, glycogenesis, and ketogenesis. In the absence of insulin, the release of free fatty acids from adipocytes increases production of ketone bodies by the mitochondria of the liver that exceeds peripheral use. Accumulation of ketone bodies causes a drop in pH and triggers the buffering system associated with metabolic acidosis. Hyperketonemia may result from impaired use of ketones by peripheral tissue, which permits strong organic acids to circulate freely. Bicarbonate buffering then does not occur and the individual develops a metabolic acidosis.

HHNKS differs from DKA in the degree of insulin deficiency (more profound I DKA) and the elevation of glucose levels and degree of fluid deficiency which are more marked in HHKS.

The basic underlying mechanism of HHS is a relative reduction in effective circulating insulin with a concomitant rise in counterregulatory hormones. Unlike patients with DKA, most patients with HHS do not develop significant ketoacidosis. Insulin remains available in amounts sufficient to inhibit lipolysis and ketogenesis but insufficient to prevent hyperglycemia. Hyperosmolarity itself may also decrease lipolysis, limiting the amount of free fatty acids available for ketogenesis.

Patients with HHS have a very high serum glucose concentration, a near normal serum bicarbonate level and pH, a serum osmolarity that is usually greater than 320 mOsm/L (normal 275–295 mOsm/L), and either absent or low levels of ketones in both the urine and serum. Electrolyte imbalances are common, with severe potassium deficits that need to be corrected, usually over several days. Phosphorous and sodium replacement may also be needed.

Cushing’s syndrome is a rare disease that is caused by the over production of cortisol by the adrenal glands. This can be caused by a tumor of the adrenal glands, the lungs, or the pituitary gland. When the tumor produces too much ACTH, it causes over production of cortisol by the adrenal glands. If the source is the pituitary, it is called Cushing’s disease. Cushing’s disease occurs more often in women than men and more often occurs between the ages of 20 and 40.

ACTH dependent hypercortisolism, the excess ACTH stimulates excess production of cortisol and loss of the negative feedback control of ACTH secretion. People with Cushing’s syndrome do not have diurnal or circadian secretion patterns of ACTH and cortisol, and they do not increase ACTH and cortisol secretion in response to stressors.

Primary hyperaldosteronism can be caused by either hyperactivity in one adrenal gland (unilateral disease) or both (bilateral disease). Unilateral disease is usually caused by an aldosterone producing adenoma (benign tumor) and less commonly by adrenal cancer or hyperplasia (when the whole gland is hyperactive). Excessive autonomous secretion of aldosterone without its principle regulator, angiotension II, causes hypokalemia and induces insulin resistance; promotes inflammation, endothelial dysfunction, and cardiovascular remodeling (increased left ventricular wall and carotid intima thickness. It also affects adipose tissue differentiation and function. Therefore, primary hyperaldosteronism can influence the features of metabolic syndrome, including hypertension, obesity, dyslipidemia, insulin resistance and hyperglycemia.

There are very complex interactions that result in the development of Type II diabetes. The pathophysiology of type 2 diabetes mellitus is characterized by peripheral insulin resistance, impaired regulation of hepatic glucose production, and declining β-cell function, eventually leading toβ -cell failure. Type 2 diabetes mellitus consists of a constellation of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. It is often associated with obesity.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). There are 2 major forms: Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP]). Nephrogenic DI characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney.

AVP is the primary determinant of free water excretion in the body. Its main target is the kidney, where it acts by altering the water permeability of the cortical and medullary collecting tubules. Water is reabsorbed by osmotic equilibration with the hypertonic interstitium and returned to the systemic circulation.

Hyperthyroidism is a set of disorders that involve excessive synthesis and secretion of thyroid hormones T3 and T4. This unregulated release causes a hypermetabolic state that can lead to a serious condition called thyrotoxicosis. The thyroid gland is regulated by thyroid stimulating hormone (TSH) from the pituitary gland, which, in turn, is regulated by the hypothalamus via a negative feedback loop. Calcitonin, a hormone that affects blood calcium levels, is also secreted by the thyroid gland. Hyperthyroidism is known as Graves’ Disease. Genetic factors interacting with the environment triggers play an important role in the pathogenesis. It is classified as an autoimmune disease and often goes along with other autoimmune diseases. It results  from a failure of the feedback system. Normally, the secretion of thyroid hormone is controlled by a complex feedback mechanism involving the interaction of stimulatory and inhibitory factors (see the image below). Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the pituitary to release TSH. In Graves’ disease, a circulating autoantibody against the thyrotropin receptor provides continuous stimulation of the thyroid gland. This stimulatory immunoglobulin has been called long-acting thyroid stimulator (LATS), thyroid-stimulating immunoglobulin (TSI), thyroid-stimulating antibody (TSab), and TSH-receptor antibody (TRab). These antibodies stimulate the production and release of thyroid hormones and thyroglobulin.

Thyroid storm is a hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis. Individuals may be undiagnosed or undertreated when they develop the symptoms. The symptoms are caused by the sudden release and action of thyroxine (T4) and triiodothyronine (T3) that exceeds metabolic demands. Symptoms must be rapidly treated in order to prevent life threatening complications such as high output heart failure, hyperthermia, delirium and hypovolemia from excessive vomiting.

Patients with primary hypothyroidism have elevated TSH levels and decreased free hormone levels. Patients with elevated TSH levels (usually 4.5- 10.0 mIU/L) but normal free hormone levels or estimates are considered to have mild or subclinical hypothyroidism. The most common cause of hypothyroidism is autoimmune thyroiditis known as Hashimoto’s disease. Primary hypothyroidism is essentially the only disease that is characterized by sustained rises in TSH levels. As the TSH level increases early in the disease, conversion of T4 to T3 increases, maintaining T3 levels. In early hypothyroidism, TSH levels are elevated, T4 levels are normal to low, and T3 levels are normal.

In a patient with underlying hypothyroidism, inciting factors responsible for developing myxedema coma are numerous and include infection, trauma, cold exposure, or medications such as sedatives and anesthetics. Although most individuals are not comatose, they are at risk for significant cardiovascular and pulmonary complications. Patients will exhibit severe hypothermia without shivering, hypoventilation, hypotension, hypoglycemia, lactic acidosis ad coma.

Pheochromocytoma is an endocrine tumor of the adrenal gland that continuously secretes catecholamines (epinephrine and norepinephrine) in an uncontrolled fashion. Hypertension results from increase peripheral vascular resistance and may be sustained or paroxysmal. Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threatening hypertension or cardiac arrhythmias. Hypermetabolism and sweating are related to chronic activation of sympathetic receptors in adipocytes, hepatocytes and other tissue. Glucose intolerance may happen because of catecholamine induced inhibition of insulin release by the pancreas.

Catecholamines produced by pheochromocytomas are metabolized within chromaffin cells. Norepinephrine is metabolized to normetanephrine and epinephrine is metabolized to metanephrine. Because this process occurs within the tumor, independently of catecholamine release, pheochromocytomas are best diagnosed by measurement of these metabolites rather than by measurement of the parent catecholamines.

Preoperative blockade of hormonally functional pheochromocytoma and paraganglioma (PPGL) to prevent cardiovascular complications is recommended, along with preoperative medical treatment to normalize blood pressure and heart rate and a  high-sodium diet with fluid intake to prevent severe hypotension after removal of the tumor. Blood pressure, heart rate, and glucose levels should be monitored immediately after surgery.

Minimally invasive (e.g., laparoscopic) adrenalectomy should be performed for most adrenal pheochromocytomas, with open resection reserved for very large or invasive pheochromocytomas; open resection is suggested for paragangliomas, but laparoscopic resection is an option for smaller tumors; partial adrenalectomy is also an option for certain patients.

Surgical resection of the tumor is the treatment of choice for pheochromocytoma and usually results in cure of the hypertension. Careful preoperative management is required to control blood pressure, correct fluid volume, and prevent intraoperative hypertensive crises.