Diabetes mellitus is a common disorder characterized by an insufficient secretion of insulin or insulin-resistance by the major target tissues (skeletal muscle, liver, and adipocytes). A severe metabolic acidosis may develop in uncontrolled diabetes mellitus.

Acidosis occurs because insulin deficiency leads to decreased glucose utilization, a diversion of metabolism toward the utilization of fatty acids, and an overproduction of ketone body acids (acetoacetic acid and _-hydroxybutyric acids). Ketone body acids are fairly strong acids (pKa 4 to 5); they are neutralized in the body by HCO3_ and other buffers. Increased production of these acids leads to a fall n plasma [HCO3 _], an increase in plasma anion gap, and a fall in blood pH (acidemia).

Severe acidemia, whatever its cause, has many adverse effects on the body. It impairs myocardial contractility, resulting in a decrease in cardiac output. It causes arteriolar dilation, which leads to a fall in arterial blood pressure. Hepatic and renal blood flows are decreased. Reentrant arrhythmias and a decreased threshold for ventricular fibrillation can occur. The respiratory muscles show decreased strength and fatigue easily. Metabolic demands are increased due, in part, to activation of the sympathetic nervous system, but at the same time anaerobic glycolysis and ATP synthesis are reduced by acidemia. Hyperkalemia is favored and protein catabolism is enhanced. Severe academia causes impaired brain metabolism and cell volume regulation, leading to progressive obtundation and coma.

An increased acidity of the blood stimulates pulmonary ventilation, resulting in a compensatory lowering of alveolar and arterial blood PCO2. The consequent reduction in blood [H2CO3] acts to move the blood pH back toward normal. The labored, deep breathing that accompanies severe uncontrolled diabetes is called Kussmaul's respiration. The kidneys compensate for metabolic acidosis by reabsorbing all the filtered HCO3 _. They also increase the excretion of titratable acid, part of which is comprised of ketone body acids. But these acids can only be partially titrated to their acid form in the urine because the urine pH cannot go below 4.5. Therefore, ketone body acids are excreted mostly in their anionic form; because of the requirement of electroneutrality in solutions, increased urinary excretion of Na_ and K_ results.

An important compensation for the acidosis is increased renal synthesis and excretion of ammonia. This adaptive response takes several days to fully develop, but it allows the kidneys to dispose of large amounts of H_ in the form NH4.The NH4_ in the urine can replace Na_ and K_ ions, resulting in conservation of these valuable cations.

The severe acidemia, electrolyte disturbances, and volume depletion that accompany uncontrolled diabetes mellitus may be fatal. Addressing the underlying cause, rather than just treating the symptoms best achieves correction of the acid-base disturbance. Therefore, the administration of a suitable dose of insulin is usually the key element of therapy. In some patients with marked acidemia (pH 7.10), NaHCO3 solutions may be infused intravenously to speed recovery, but this does not correct the underlying metabolic problem. Losses of Na_, K_, and water should be replaced.


Source by Tora Fallen