1. Introduction
DKA occurs due to interplay between absolute or relative deficiency of insulin and counterregulatory hormones (excess). The former leads
... [Show More] to hyperglycemia and ketosis, while the latter
(epinephrine, cortisol and growth hormone) released in response to stress, aggravates
hyperglycemia by blocking the action of insulin and enhancing glycogenolysis in the liver.
When blood glucose levels exceed the renal threshold (180mg/dL), glycosuria occurs. The
resultant osmotic diuresis leads to volume depletion and dehydration, which activates the reninangiotensin-aldosterone axis and also triggers the release of counter-regulatory hormones. These
hormones act towards preserving the intravascular volume.
Vomiting, due to stimulation of chemoreceptor trigger zone by hydrogen ions and ketones, further
aggravates volume loss and dehydration.
DKA may occur at diabetes onset or in children with established diabetes who have either omitted
insulin or had inadequate insulin therapy during intercurrent illness.
DKA carries a mortality rate of 0.3–0.5% in developed economies and much higher in developing
economies.
The biochemical criteria for the diagnosis of DKA are:
Hyperglycemia (blood glucose >11mmol/L),>200mg/dl
Venous pH <7.3 and / or bicarbonate <15mmol/L.
Ketonaemia (indicated by blood beta-hydroxybutyrate above 3 mmol/litre)
Ketonuria and glycosuria. Urine ketones are typically ≥2+ (“moderate or large”) positive.
Partially treated children and children who have consumed little or no carbohydrate may,
rarely, have only modestly elevated blood glucose concentrations, referred to as
"euglycemic ketoacidosis" . This can be caused by starvation (anorexia or religious fasting)
, a low carbohydrate high fat diet.
There is also: an increased ion gap and an elevated effective serum osmolality, indicating
hypertonic dehydration.
Anion gap = Na – (Cl + HCO3); Normal = 12 ± 2. In DKA the anion gap is
typically 20-30 mmol/L; an anion gap >35 mmol/L suggests concomitant
lactic acidosis
Corrected Na (Na correction for glucose) = Measured Na + 2x {(Glucose
– 5.5) ÷ 5.5} mmol/L = measured Na + (serum glucose-100) (1.6)/100
Effective osmolality = 2 x (Na (uncorrected) + K) + Glucose mmol/L =
2(Na+K) + glucose/18 + BUN/2.8. is frequently in the range of 300-350
mmol/Kg.
Clinically they may have the following features:
Acetone-fruity breath or Kussmaul respirations
Dehydration, decreased peripheral perfusion/hypovolemic shock (rarely)
Nausea and/or vomiting, abdominal pain
Fatigued, blurry vison, confusion, drowsiness, progressive decrease in level of
consciousness and, eventually, loss of consciousness (coma).
The clinical manifestations of DKA are related to the degree of hyperosmolality, volume depletion,
and severity of acidosis
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1.1. Precipitating causes:
Infection;
Psychosocial: Stress…
Omission of insulin;
Drugs like Steroids
Deficient patient/parent/school education
Health service problems and so on.
1.2. Potential pitfalls in diagnosis:
Children may appear well despite gross metabolic imbalance
Abdominal symptoms may mimic an acute abdomen
DKA can occur without pronounced hyperglycemia
Hyperglycaemia may cause false hyponatraemia
Creatinine assay may be falsely elevated by ketones (i.e. aceto-acetate)
Outdated reagent strips may not show ketones
1.3. Pathophysiology of DKA(From: ISPAD 2018)
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1.4. Classification of Ketoacidosis:
NORMAL MILD MODERATE SEVERE
CO2 (mEq/L,
venous)
20-28 16-20 10-15 <10
pH (venous) 7.35-7.45 7.25-7.35 7.15-7.25 <7.15
Clinical No change Oriented, alert
but
fatigued
Kussmaul
respirations;
oriented
but sleepy;
arousable
Kussmaul or
depressed
respirations;
sleepy to
depressed
sensorium to
coma
Hydration NORMAL < 5% DHN 5 to 7%DHN 7 to 10% DHN
In Shock:: (>10% dehydration: shock, weak peripheral pulses, hypotension, oliguria;
which is rare in DKA)
Classification of severity of DKA based on acidosis may be difficult in our set up due to lack of the
facility to measure venous PH and Bicarbonate; but can be assumed based on Clinical condition
of the patient, i.e. : Level of consciousness, Level of DHN, Breathing pattern…
At the time of presentation, clinical estimates of the extracellular fluid volume deficit in moderate to
severe DKA are usually in the range of 5 to 10 percent.
Hypovolemic shock is a rare occurrence in DKA. The patient in shock should be evaluated for
other causes of shock.
In DKA, Clinical assessment of dehydration may be difficult especially in young children and
Severity of dehydration is often overestimated; In addition, the degree of extracellular fluid loss is
in part masked because hyperglycemia results in a shift of water from the intracellular to the
extracellular fluid compartment.
Reduced skin turgor can be absent, as children with DKA tend to have a preserved intravascular
volume due to hyperosmolarity.
Additionally, the compensatory hyperventilation in response to metabolic acidosis can cause
vasoconstriction due to lowering of the vasodilator CO2 (an indirect effect) thus masquerading as
severe dehydration. It is also pertinent to remember that severe acidosis may not always correlate
with severe dehydration.
Increased serum urea nitrogen and hematocrit or hemoglobin concentration or, alternatively,
plasma albumin or total protein concentration if anemia is suspected are useful markers of the
degree of ECF contraction, and should be determined during fluid resuscitation and deficit
replacement.
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2. Management of DKA:
Management goals:
Restoration of circulating volume
Replacement of fluid and electrolyte deficit evenly over 48 hours
Correction of acidosis and hyperglycemia with insulin
Treatment of Precipitating factors
Avoidance of the complications of DKA and its treatment by frequent monitoring for
Cerebral edema
Hypoglycemia
Electrolyte abnormalities
Management background: Any treatment plan for DKA should be based on the underlying
Pathophysiology. Hyperglycemia and ketoacidosis induce important alterations in organ
Physiology. Hyperglycemia causes an osmotic diuresis and eventually leads to dehydration,
electrolyte depletion, and hypertonicity. Metabolic acidosis is partially compensated by
hyperventilation and hypocapnia. These effects in turn cause changes in Renal, CNS, and
Cardiovascular system functioning.
Considering the above, the first therapeutic step is to restore extracellular fluid volume
which has been depleted through osmotic diuresis and vomiting. Insulin must be given to
allow normal carbohydrate utilization and to stop ketogenesis. Serum hyperosmolality
should be normalized gradually and intracellular stores of potassium replenished. Severe
acid/base disturbances need to be corrected both for homeostatic reasons and to permit
optimally effective insulin action. Normal glycogen and fat stores, and protein synthesis [Show Less]