Diabetic ketoacidosis or DKA, primarily is a type I diabetes complication, occurs mainly in younger adults and people in their teenage years.
DKA can develop in a new-onset type I diabetic or a diabetic who misses insulin doses. Often it occurs with poor insulin compliance and lack of knowledge about managing insulin administration in acute illness. The patient who is feeling unwell may believe that he/she does not need insulin while not eating.
Precipitating factors include medications and drugs that affect carbohydrate metabolism such as corticosteroids, thiazides, loop diuretics, sympathomimetics, anti-hypertensives, anti-histamines, tricyclic antidepressants, alcohol, cocaine and ecstasy1 . Often DKA develops because of an acute illness or infection such as pneumonia or urinary tract infection. Pregnancy, gastroenteritis, trauma, burns, surgery, sepsis, pancreatitis, stroke and silent myocardial infarction can also provoke DKA.
The patient fails to meet the increased insulin demand when these physical stressors occur. The stressors provoke an excessive release of counterregulatory hormones such as glucagon, catecholamines, cortisol and growth hormone and the elevation of pro-inflammatory cytokines. In this ‘fight-or-flight’ stress response energy stores from fat, protein and glycogen are mobilised and new glucose is produced.
The 4 main characteristics of DKA
Insulin deficiency leads to accumulation of glucose in the blood as glucose cannot enter the cells. Normally insulin suppresses glucose production and lipolysis in the liver. Therefore insulin deficiency leads to hepatic glucose overproduction.
Counter-regulatory hormones, glucagon, cortisol and catecholamines increase the glucose level through gluconeogenesis (formation of new glucose) and glycogenolysis (breakdown of complex glycogen into simple glucose). The process of gluconeogenesis is driven by the high availability of all the precursors: amino acids (from protein breakdown), lactate (from muscle glycogenolysis), and glycerol (from increased lipolysis).
It is thought that when serum osmolality is high, even less insulin is produced and insulin resistance increases. These processes make it even more difficult for tissues to take up glucose. As a result hyperglycaemia worsens.
Ketosis and acidosis
Insulin deficiency and elevated counter-regulatory hormones promote lipolysis in adipose tissue and inhibit lipogenesis, leading to increased release of fatty acids and glycerol. The liver is stimulated by glucagon to oxidise free fatty acids to ketone bodies such as beta-hydroxybutyrate and acetoacetate. The production of ketone bodies exceeds the ability of tissues to utilise them, resulting in ketonaemia. Ketone bodies fully dissociate into ketone anions and hydrogen ions. The body attempts to maintain extracellular pH by binding the hydrogen ions with bicarbonate ions thus depleting its alkali reserves.
The respiratory system compensates for acidosis by increasing the depth and rate of breathing to exhale more carbon dioxide. This is called Kussmaul respiration. The breath has a fruity, acetone-like odour (“nail polish remover”), because the acetone ketones are exhaled.
The kidneys excrete ketone bodies (ketonuria), and large amounts of glucose spill over into the urine leading to osmotic diuresis, dehydration and haemoconcentration. This in turn causes tissue ischaemia and increased lactic acid production that worsens the acidosis. Increased acidosis causes enzymes to become ineffective and metabolism decelerates. Even fewer ketone bodies are metabolised and acidosis worsens. Acidosis can cause hypotension due to its vasodilating effect and negative effect on heart contractility.
Hyperglycaemia raises extracellular fluid osmolality. Water is drawn from the cell into the extracellular compartment and intracellular dehydration follows. Hyperosmolality is the main contributor to altered mental status, which can lead to coma. Cellular dehydration and acid overload can also affect mental status.
The development of total body dehydration and sodium depletion is the result of increased urinary output and electrolyte losses. With marked hyperglycaemia the serum glucose threshold for glucose reabsorption in the kidneys of 10mmol/L is exceeded, and glucose is excreted in urine (glucosuria). Glucosuria causes obligatory losses of water and electrolytes such as sodium, potassium, magnesium, calcium and phosphate (osmotic diuresis). Excretion of ketone anions also contributes to osmotic diuresis and causes additional obligatory losses of urinary cations (sodium, potassium and ammonium salts). Insulin deficiency per se might also contribute to renal losses of water and electrolytes, because insulin stimulates salt and water reabsorption by the nephron and phosphate reabsorption in the proximal tubule.
Acidosis can cause nausea and vomiting and this leads to further fluid loss. There is increased insensible fluid loss through Kussmaul respiration. Severe dehydration reduces renal blood flow and decreases glomerular filtration, and may progress to hypovolaemic shock.
Potassium is the electrolyte that is most affected in DKA. Acidosis causes hydrogen ions to move from the extracellular fluid into the intracellular space. Hydrogen movement into the cell promotes movement of potassium out of the cell into the extracellular compartment (including the intravascular space). Severe intracellular potassium depletion follows. As the liver is stimulated by the counterregulatory hormones to break down protein, nitrogen accumulates, causing a rise in blood urea nitrogen. Proteolysis leads to further loss of intracellular potassium and increases intravascular potassium.
The body excretes this mobilized potassium in urine by osmotic diuresis, and loses additional potassium through vomiting. Serum potassium readings can be normal or high, but this is misleading, because there is an intracellular and total body potassium deficit. Sodium, phosphate, chloride and bicarbonate are also lost in urine and vomitus. Sodium levels are “lowered” (diluted) by the movement of water from the intracellular to the extracellular space in response to hyperglycaemia.
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