Differentials

Hyperosmolar hyperglycemic state (HHS)

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SIGNS / SYMPTOMS

Patients are typically older than those with diabetic ketoacidosis (DKA) and usually have type 2 diabetes. Older nursing home residents with poor fluid intake are at high risk.

Symptoms evolve insidiously over days to weeks.[1]

Mental obtundation and coma are more frequent.[1]​ Focal neurologic signs (hemianopia and hemiparesis) and seizures are also seen.[61]​ Seizures may be the dominant clinical feature.[62]​​

INVESTIGATIONS

Serum glucose is >600 mg/dL (>33.3 mmol/L). Total serum osmolality is usually >320 mOsm/kg (>320 mmol/kg). Effective serum osmolality is >300 mOsm/kg (>300 mmol/kg).[1]

Urine ketones are normal or only mildly positive (less than 2+ on dipstick). Serum ketones are negative (beta-hydroxybutyrate concentration <3 mmol/L).

Anion gap is variable but typically <12 mEq/L (<12 mmol/L).

Total chloride deficit is 5-15 mEq/kg (5-15 mmol/kg).

ABG: arterial pH is typically ≥7.30, whereas in DKA it ranges from <7.00 to 7.30. Arterial bicarbonate is ≥15 mEq/L (≥15 mmol/L).[1]

Lactic acidosis

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The presentation is identical to that of diabetic ketoacidosis. In pure lactic acidosis, the serum glucose and ketones should be normal and the serum lactate concentration should be elevated.

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Serum lactate elevated. Hyperlactatemia is usually defined as a level of 2-5 mmol/L, whereas severe hyperlactatemia is defined as a level >5 mmol/L.[77]​ Blood glucose normal. Negative plasma ketones (beta-hydroxybutyrate concentration <3 mmol/L).[13]

Starvation ketosis

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Starvation ketosis results from inadequate carbohydrate availability resulting in physiologically appropriate lipolysis and ketone production to provide fuel substrates for muscle. Condition develops over many days and is suggested by a prolonged history of dietary intake <2090 kJ/day (500 kcal/day).[1]

INVESTIGATIONS

Blood glucose is usually normal.[13]​ Although the urine can have large amounts of ketones, the blood rarely does. Arterial pH is normal and the anion gap is at most mildly elevated.[13]​ Serum bicarbonate concentration usually >18 mEq/L (>18 mmol/L) due to renal compensation.[9]​ If electrolyte intake is also limited, then electrolyte disturbances will eventually occur.​[9]

Alcoholic ketoacidosis

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Classically, these are people with longstanding alcohol use disorder for whom ethanol has been the main caloric source for days to weeks. The ketoacidosis occurs when for some reason alcohol and caloric intake decreases (such as a recent binge culminating in vomiting and acute starvation).[1]

INVESTIGATIONS

Ketoacidosis without hyperglycemia in a patient with long-standing alcohol use is virtually diagnostic of alcoholic ketoacidosis.[9]​ Total ketone bodies are much greater than in diabetic ketoacidosis, with a higher beta-hydroxybutyrate to acetoacetate ratio of 7:1, versus 3:1 in DKA.[13]

Salicylate poisoning

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Can be differentiated by history and laboratory investigation. Salicylate intoxication produces an anion gap metabolic acidosis usually with a respiratory alkalosis.

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Plasma glucose is normal or low, ketones are negative, osmolality is normal, and salicylates are positive.[13]​ 

Ethylene glycol/methanol intoxication

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Methanol and ethylene glycol also produce an anion gap metabolic acidosis without hyperglycemia or ketones.

INVESTIGATIONS

Methanol/ethylene glycol serum levels are elevated. They can produce an increase in the measured serum osmolality.[13] Blood glucose normal. Negative plasma ketones (beta-hydroxybutyrate concentration <3 mmol/L).[13]​​

Uremic acidosis

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Uremia can develop with chronic kidney disease, especially the later stages, or with acute kidney injury if loss of kidney function is rapid. Uremic symptoms include fatigue, anorexia, nausea, vomiting, pruritus, metallic taste, restless legs, and altered mental status. Physical exam findings such as asterixis and pericardial rub (due to uremic pericarditis), among others, may be noted.[78]

INVESTIGATIONS

Normal blood glucose and negative plasma ketones (beta-hydroxybutyrate concentration <3 mmol/L).[13]​ Markedly elevated BUN (usually >200 mg/dL [>71.4 mmol/L]) and elevated creatinine.[13]​ pH and anion gap are usually mildly abnormal.[13]​​

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