Ketosis ketoacidosis caused

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

Higher than normal quantities of ketone bodies present in the blood or urine constitute ketonemia (hyperke-tonemia) or ketonuria, respectively. The overall condition is called ketosis. Acetoacetic and 3-hydroxybutyric acids are both moderately strong acids and are buffered when present in blood or other tissues. However, their continual excretion in quantity progressively depletes the alkah reserve, causing ketoacidosis. This may be fatal in uncontrolled diabetes mellitus. 

Diabetic ketoacidosis A reversible but life-threatening short-term complication primarily seen in patients with type 1 diabetes caused by the relative or absolute lack of insulin that results in marked ketosis and acidosis. 

Hyperosmolar hyperglycemic state A potentially fatal short-term complication most commonly seen in older patients with type 2 diabetes caused by an insufficiency of insulin action that leads to alterations of osmolality and hyperglycemia, but without the ketosis and acidosis seen in diabetic ketoacidosis. 

The three compounds, acetoacetate, acetone, and 3-hydroxybutyrate, are known as ketone bodies.60b The inability of the animal body to form the glucose precursors, pyruvate or oxaloacetate, from acetyl units sometimes causes severe metabolic problems. The condition known as ketosis, in which excessive amounts of ketone bodies are present in the blood, develops when too much acetyl-CoA is produced and its combustion in the critic acid cycle is slow. Ketosis often develops in patients with Type I diabetes mellitus (Box 17-G), in anyone with high fevers, and during starvation. Ketosis is dangerous, if severe, because formation of ketone bodies produces hydrogen ions (Eq. 17-5) and acidifies the blood. Thousands of young persons with insulin-dependent diabetes die annually from ketoacidosis. 

Hyperosmolar diabetic coma occms chiefly in noninsulin-dependent diabetics who fail to compensate for their continuing, osmotic glucose diuresis. It is characterised by severe dehydration, a very high blood sugar (> 33 mmol/1 600 mg/100 ml) and lack of ketosis and acidosis. Treatment is with isotonic (0.9%) saline, at half the rate recommended for ketoacidotic coma, and with less potassium than in severe ketoacidosis. Insulin requirements are less than in ketoacidosis, where the acidosis causes resistance to the actions of insuhn, and should generally be half those shown in Table 35.2. Patients are more liable to thrombosis and prophylactic heparin is used. 

Two of the ketone bodies are acids, and their accumulation in the blood as ketosis worsens results in a condition of acidosis called ketoacidosis because it is caused by ketone bodies in the blood. If ketoacidosis is not controlled, the person becomes severely dehydrated because the kidneys excrete excessive amounts of water in response to low blood pH. Prolonged ketoacidosis leads to general debiUtation, coma, and even death. 

Conditions that result in increased production of metabolic acids include lactic acidosis and diabetic ketoacidosis. Lactic acidosis occurs with anaerobic metaboUsm in the presence of severe hypoxemia (i.e., Pao < 36 mm Hg). Any condition that prevents adequate oxygenation resulting in hypoxemia, such as respiratory failure or lung cancer, as well as any condition causing a decrease in perfusion to body tissues, such as heart failure or shock of any form, will result in anaerobic metabolism and lactic acid buildup. In diabetic ketoacidosis, the lack of insulin to move glucose into the cells results in a form of starvation and the production and accumulation of ketoacids (i.e., ketosis) owing to the use of lipids for fuel. 

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