Diabetic Ketoacidosis (DKA): Symptoms, Causes, Criteria, DKA Pathophysiology and Management

Diabetic Ketoacidosis Epidemiology

DKA is the commonest acute metabolic complication seen in the emergency room responsible for 20-30% of the Diabetes mellitus admissions. In the National Diabetes Study Group data from the USA, it was noted that there were 3-8 episodes per 1000 DM patients with 20 30% of the cases occurring in new diabetics. It has also been documented that it is commoner in black men than white men. DKA Mortality is relatively high accounting for 10% in the United Kingdom between 1970 and 1978. In Europe and America, DKA cases are about 10 to 30 per 100,000 of the population. Diabetic ketoacidosis is commoner in females than males and has a higher mortality rate in the elderly.

DKA Definition and Meaning

Diabetic Ketoacidosis (DKA) is an acute metabolic complication of Diabetes mellitus that is often characterized by Hyperglycemia of >300mg/dL, Acidosis , blood pH <7.3 and increased total blood ketones of > 5 mmol/L. In clinical practice, DKA is suspected when there is ketonuria++ in the face of hyperglycemia. DKA patients appear severely ill, often very dehydrated, and have rapid deep breathing with the odor of acetone in their breath (Kussmaul respiration). Hypotension, tachycardia, and abdominal pain are common; when left untreated, they progress through mental stupor to coma and death.

DKA was formerly considered as a hall mark of type 1 Diabetes mellitus but currently it is known that some type 2 diabetes mellitus patients who are being treated by oral hypoglycemic agent may also develop DKA.

Diabetic Ketoacidosis Pathophysiology

DKA Signs and Symptoms

1. Polyuria
2. Polydipsia
3. Anorexia
4. Vomiting
5. Abdominal cramps
6. Weight loss
7. Leg cramps
8. Dehydration
9. Hypotension
10. Tachycardia (fast heart beat)
11. Hyperventilation (Fast breathing)
12. Hypothermia
13. Delirium
14. Coma

Diabetic Ketoacidosis Pathogenesis (DKA Pathophysiology)

Diabetic Ketoacidosis (DKA) occurs as a result of absolute or relative lack of insulin. In the relative lack of insulin, there is elevation of counter regulatory hormones like glucagon, cortisol, catecholamines and growth hormone; these hormones oppose the function of insulin and their increase often overwhelm insulin action and DKA occurs. When these hormones overwhelm insulin, there is increase in the catabolic reactions of the body with the promotion of lipolysis, increased fatty acid oxidation and the production of acetyl CoA, acetoacetyl CoA and eventually ketone bodies are produced – acetoacetate, 3-hydroxybutyrate and acetone. Carbohydrate and protein metabolism are also affected leading to gluconeogenesis, glycogenolysis, increased hepatic glucose production, reduced protein synthesis, wasting and rapidly increasing hyperglycemia. When there is Ketoacidosis, the respiratory center of the brain is stimulated and Kussmaul breathing occurs. The Urine becomes acidic and osmotic diuresis occurs with the Hydrogen, Potassium and Sodium ions being lost in the urine together with ketones.

Diabetic Ketoacidosis Management Guidelines and Diagnostic Tests

Diabetic Ketoacidosis Criteria for Diagnosis (DKA Criteria)

1. Hyperglycaemia 300mg% (16.7mmol/L); though some researchers have lowered the value to 250mg% in recent publications. Glycosuria often 3-4+.
2. Hyperketonaemia (b- hydroxybutyrate and acetoacetate) of > 5mmol/L. This often manifests with heavy ketonuria.
3. Acidosis with blood PH < 7.3 and serum bicarbonate < 15meq/L (Normal pH 7.4 0.05)

DKA Precipitating Factors (Causes of DKA)

1. Infection
2. Omission of insulin doses
3. Trauma
4. Surgery
5. Excessive alcohol ingestion
6. Cardiovascular accident (CVA)
7. Myocardial infarction
8. Gangrene such as gas gangrene and Fourniers gangrene.

Diabetic Ketoacidosis Tests

1. Urinalysis: there will be glycosuria of 4+ and Ketonuria 2+ to 4+
2. Blood sugar levels of greater than 300mg%
3. Blood pH < 7.3
4. Elevated serum Ketones of more than 5mmol/L
5. Hyperphosphataemia
6. Hyperkalemia (K+ may be high or normal despite reduction in total body potassium)
7. Hematology may show a PCV that may be normal or high
8. White cell count may be normal or high
9. Urine MCS to check for infections since infection is a risk factor for precipitating DKA
10. ECG to check for the status of the heart

Guidelines and Precautions when carrying out DKA Laboratory Tests

Diabetic Ketoacidosis tests could be done in order to confirm diagnosis, or elicit precipitating cause or demonstrate any complications. It is important to recognize that in diabetic ketoacidosis the major ketone body in the serum is beta hydroxybutyrate with lesser amounts of acetoacetate what this means is that only acetoacetate is detected by the nitroprusside reaction (Acetest, Ketostix). This can be misleading if serum is being tested by the nitroprusside reaction such as during circulatory collapse, the formation of lactic acid can shift the redox state to increase production of beta hydroxybutyrate at the expense of the detectable acetoacetate. It is therefore possible to have severe diabetic ketoacidosis with only a slightly positive serum nitroprusside reaction.

There is elevation of serum amylase of salivary and pancreatic origin in diabetic ketoacidosis and since there is abdominal pain in DKA this elevation of serum amylase might be mistaken as a diagnosis of acute pancreatitis.

The serum creatinine levels in Diabetic ketoacidosis are usually elevated because of dehydration, but also because acetoacetate will give a positive interference in its estimation by the Jaffe reaction. Hence serum creatinine concentrations when measured by the above method are not a reliable guide to renal function early in the disease process.

DKA Management Guidelines

1. Admission is compulsory for a patient presenting with DKA
2. 4 to 6 liters of Normal saline are given over 24hrs at the rate of 1 Liter in 30 min, then 1 Liter in 1hr, 1 Liter in 2hr and 1 Liter at 4 hourly intervals until about 4 to 6 liters have been given.
3. Give soluble insulin by giving 10 units Stat dose via Intravenous route and 6 units every hour via intravenous route until the blood sugar levels falls to 250mg% then replace normal saline with 5% Dextrose water with 5 units insulin.
4. Bicarbonate should be given occasionally
5. Treat any infection
6. Correct any underlying precipitant of DKA
7. Potassium replacement

Complications of DKA (Diabetic Ketoacidosis Complications)

1. Cerebral edema occurs in 1% to 5% of cases of DKA. Cerebral edema is the most serious complication of DKA and has mortality rate of 20% to 80%
2. Intracranial thrombosis or infarction
3. Acute tubular necrosis with acute renal failure as a result of severe dehydration
4. Pancreatitis
5. Arrhythmias as a result of electrolyte abnormalities
6. Pulmonary edema
7. Bowel ischemia
8. Peripheral edema may occur commonly about 24 to 48 hours after therapy is initiated and this could be related to residual elevations in antidiuretic hormone and aldosterone

Differential Diagnosis of DKA

1. Alcoholic ketoacidosis or starvation
2. Uremia
3. Salicylate or methanol poisoning
4. Renal or gastrointestinal bicarbonate losses due to diarrhea or renal tubular acidosis
5. Hyperosmolar non-ketotic coma (HONK)