Porth's Essentials of Pathophysiology, 4e

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Endocrine System

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The treatment of HHS requires judicious medical observation and care as water moves back into brain cells, posing a threat of cerebral edema. Extensive potas- sium losses that also have occurred during the diuretic phase of the disorder require correction. Because of the problems encountered in the treatment and the serious nature of the disease conditions that cause HHS, the prognosis for this disorder is less favorable than that for ketoacidosis. Hypoglycemia Hypoglycemia, or an insulin reaction, occurs from a rel- ative excess of insulin in the blood and is characterized by below-normal blood glucose levels. 43,44 It occurs most commonly in people treated with insulin injections, but prolonged hypoglycemia also can result from some oral hypoglycemic agents (i.e., sulfonylurea). There are many factors that can precipitate an insulin reaction in a per- son with type 1 or type 2 diabetes, including error in insulin dose, failure to eat, increased exercise, decreased insulin need after removal of a stress situation, medi- cation changes, and a change in insulin injection site. Alcohol decreases liver gluconeogenesis, and people with diabetes need to be cautioned about its potential for causing hypoglycemia, especially if it is consumed in large amounts or on an empty stomach. Hypoglycemia usually has a rapid onset and progres- sion of symptoms. The signs and symptoms of hypo- glycemia can be divided into two categories: (1) those caused by altered cerebral function and (2) those related to activation of the autonomic nervous system. Because the brain relies on blood glucose as its main energy source, hypoglycemia produces behaviors related to altered cerebral function. Headache, difficulty in prob- lem solving, disturbed or altered behavior, coma, and seizures may occur. At the onset of the hypoglycemic episode, activation of the parasympathetic nervous sys- tem often causes hunger. The initial parasympathetic response is followed by activation of the sympathetic nervous system; which causes anxiety, tachycardia, sweating, and a cool and clammy skin due to constric- tion of the skin vessels. The signs and symptoms of hypoglycemia are highly variable, especially in children and the elderly, and not everyone manifests all or even most of the symptoms. Elderly people may not display the typical autonomic responses, but typically do display signs of altered cere- bral function, including mental confusion. Also, some medications, such as β -adrenergic blocking drugs, interfere with the autonomic response normally seen in hypoglycemia. Some people develop hypoglycemic unawareness; that is, they do not report symptoms when their blood glucose concentrations are less than 50 to 60 mg/dL (2.8 to 3.3 mmol/L). This occurs most commonly in people who have a longer duration of dia- betes and A1C levels within the normal range. 43 The most effective treatment of an insulin reaction is the immediate administration of 15 g of glucose in a concentrated carbohydrate source. According to the so-called rule of 15 , this 15 g of glucose can be repeated

administration of insulin and intravenous fluid and elec- trolyte replacement solutions. Because insulin resistance accompanies severe acidosis, low-dose insulin therapy is used. An initial loading dose of short-acting (i.e., regu- lar) or rapid-acting insulin often is given intravenously, followed by continuous low-dose short-acting insulin infusion. Frequent laboratory tests are used to moni- tor blood glucose and serum electrolyte levels and to guide fluid and electrolyte replacement. It is important to replace fluid and electrolytes and correct pH while bringing the blood glucose concentration to a normal level. Too rapid a drop in blood glucose may cause hypo- glycemia. A sudden change in the osmolality of extracel- lular fluid can also occur when blood glucose levels are lowered too rapidly, and this can cause cerebral edema. Cerebral and other autoregulatory mechanisms may not be as well developed in younger children, placing them at particular risk for development of cerebral edema. 42 Serum potassium levels often fall as acidosis is corrected and potassium moves from the extracellular into the intracellular compartment. Thus, it may be necessary to add potassium to the intravenous infusion. Identification and treatment of the underlying cause, such as infection, also are important. Hyperglycemic Hyperosmolar State The hyperglycemic hyperosmolar state (HHS) is char- acterized by hyperglycemia (blood glucose >600 mg/dL [33.3 mmol/L]), hyperosmolarity (plasma osmolarity >320 mOsm/L) and dehydration, the absence of ketoaci- dosis, and depression of the sensorium. 40 Hyperglycemic hyperosmolar state may occur in various conditions, including type 2 diabetes, acute pancreatitis, severe infec- tion, myocardial infarction, and treatment with oral or parenteral nutrition solutions. It is seen most frequently in people with type 2 diabetes. A partial or relative insu- lin deficiency may initiate the syndrome by reducing glucose utilization while inducing a glucagon-stimulated increase in hepatic glucose output. With massive glycos- uria, obligatory water loss occurs. If the person is unable to maintain adequate fluid intake because of associated acute or chronic illness or has excessive fluid loss, dehy- dration develops. As the plasma volume contracts, renal insufficiency develops and the resultant limitation of renal glucose losses leads to increasingly higher blood glucose levels and an increase in severity of the hyper- osmolar state. In hyperosmolar states, the increased serum osmo- larity has the effect of pulling water out of body cells, including brain cells. The condition may be complicated by thromboembolic events arising because of the high serum osmolality. The most prominent manifestations are weakness, dehydration, polyuria, neurologic signs and symptoms, and excessive thirst. The neurologic signs include hemiparesis, Babinski reflex, aphasia, muscle fasciculations, hyperthermia, hemianopia, nys- tagmus, visual hallucinations, seizures, and coma. The onset of HHS often is insidious, and because it occurs most frequently in older people, it may be mistaken for a stroke.