Porth's Essentials of Pathophysiology, 4e

811

Diabetes Mellitus and the Metabolic Syndrome

C h a p t e r 3 3

Insulin deficiency (and glucagon excess)

Decreased glucose uptake

Lipolysis

Glycogen

Protein breakdown

Glycerol FFA

Ketones

Gluconeogenesis

Amino acids

Glucose

FIGURE 33-10. Mechanisms of diabetic ketoacidosis. Diabetic ketoacidosis is associated with very low insulin levels and extremely high levels of glucagon, catecholamines, and other counterregulatory hormones. Increased levels of glucagon and the catecholamines lead to mobilization of substrates for gluconeogenesis and ketogenesis by the liver. Gluconeogenesis in excess of that needed to supply glucose to the brain and other glucose- dependent tissues produces a rise in blood glucose levels. Mobilization of free fatty acids (FFAs) from triglyceride stores in adipose tissue leads to accelerated ketone production and ketosis. CNS, central nervous system.

Metabolic acidosis

Hyperglycemia

Osmotic diuresis

CNS depression

Coma

Water, electrolyte loss

Dehydration

Circulatory failure

rapid breakdown of energy stores from muscle and fat deposits, leading to increased movement of amino acids to the liver for conversion to glucose and of fatty acids for conversion to ketones. In the presence of ketosis, the levels of glucagon and counterregulatory hormones (i.e., glucocorticosteroids, epinephrine, and growth hor- mone) are consistently increased. Furthermore, in the absence of insulin, peripheral utilization of glucose and ketones is reduced. Metabolic acidosis is caused by the excess ketoacids that require buffering by bicarbonate ions; this leads to a marked decrease in serum bicarbon- ate levels. The definitive diagnosis of DKA consists of hyperglycemia (blood glucose levels >250 mg/dL [13.8 mmol/L]), low serum bicarbonate, low arterial pH, and positive urine and serum ketones. It can be further subdivided into mild DKA (serum bicarbon- ate of 15 to 18 mEq/dL [15 to 18 mmol/L], pH 7.25 to 7.30); moderate DKA (serum bicarbonate 10 to <15 mEq/dL [10 to <15 mmol/L], pH 7.00 to 7.24); and severe DKA (serum bicarbonate <10 mEq/dL [<10 mmol/L], pH <7.00). 40,41 Hyperglycemia leads to osmotic diuresis, dehydration, and a critical loss of electrolytes. Hyperosmolality of extracellular flu- ids from hyperglycemia leads to a shift of water and potassium from the intracellular to the extracellular

compartment. Extracellular sodium concentration fre- quently is low or normal despite enteric water losses because of an intracellular–extracellular fluid shift. This dilutional effect is referred to as pseudohypona- tremia. Serum potassium levels may also be normal or elevated, despite total potassium depletion resulting from protracted polyuria and vomiting. The development of DKA is commonly preceded by a day or more of polyuria, polydipsia, nausea, vomiting, and marked fatigue, with eventual stupor that can prog- ress to coma. Abdominal pain and tenderness may be experienced without abdominal disease. The breath has a characteristic fruity smell because of the presence of volatile ketoacids. 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 vol- ume, and the rate and depth of respiration increase (i.e., Kussmaul respiration) as the body attempts to prevent further decreases in pH. Metabolic acidosis is discussed further in Chapter 8. The goals in treating DKA are to improve circulatory volume and tissue perfusion, decrease blood glucose, and correct the acidosis and electrolyte imbalances. These objectives usually are accomplished through the