DKA Flashcards
What is DKA?
Diabetic ketoacidosis (DKA)
- is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus
- less commonly, it can occur in children with type 2 diabetes mellitus
What is the cause of DKA?
is caused by absolute or relative insulin deficiency
Epidemiology of DKA?
occurs in 20-40% of children with:
1. new-onset diabetes
2. known diabetes who omit insulin doses or who do not successfully manage an intercurrent illness
Definition of DKA?
hyperglycemia + metabolic acidosis + ketosis
Hyperglycemia?
Blood glucose of >200 mg/dL (11 mmol/L)
Metabolic acidosis?
- a venous pH <7.3
or - plasma bicarbonate <15 mEq/L (15 mmol/L)
Ketosis?
Determined by the presence of ketones in the blood or urine
>3 mmol
Problems with measuring ketosis?
Standard qualitative measurements of ketones (as acetoacetate) can underestimate severity of ketosis
How to accurately measure ketosis?
Serum beta-hydroxybutyrate is a more accurate measure of ketosis and should be used whenever available
- Beta-hydroxybutyrate concentrations ≥3 mmol/L (31 mg/dL) are consistent with DKA
What is the fasted state?
occurs when you have not eaten for 10-12 hours prior to exercise resulting in a decrease of insulin levels leading to a catabolic state
What is a catabolic state?
breaking down or losing overall mass, both fat and muscle
What is a postprandial state?
occurs after meal ingestion and embodies the digestion and absorption of nutrients and is characterized by increase in insulin level resulting in an anabolic state
What is an anabolic state?
where the body builds and repairs muscle tissue
What is T1 diabetes mellitus?
is a progressive low-insulin catabolic state in which feeding does not reverse but rather exaggerates these catabolic processes
Influence of high plasma insulin (postprandial state) on the liver?
- glucose uptake
- glycogen synthesis
- lipogenesis
- absence of gluconeogenesis
- absence of ketogenesis
Influence of low plasma insulin (fasted state) on the liver?
- glucose production
- glycogenolysis
- absence of lipogenesis
- gluconeogenesis
- ketogenesis
Influence of high plasma insulin on muscle?
- glucose uptake
- glucose oxidation
- glycogen synthesis
- protein synthesis
Influence of low plasma influence on the muscle?
- absence of glucose uptake
- fatty acid and ketone oxidation
- glycogenolysis
- proteolysis and amino acid release
Influence of high plasma insulin on adipose tissue?
- glucose uptake
- lipid synthesis
- triglyceride uptake
Influence of low plasma insulin in adipose tissue?
- absence of glucose uptake
- lipolysis and fatty acid release
- absence of triglyceride uptake
Effects of insulopenia - hyperglycemia?
- hyperglycemia
- Osmotic diuresis (> 180mg/dL; 10mmol/L)
- loss of calories and electrolytes
- persistent dehydration - Hypersecretion of stress hormones (epinephrine, cortisol, growth hormone, and glucagon)
How does insulopaenia cause hyperglycemia?
- glucose utilization by muscle and fat decreases and postprandial hyperglycemia appears
- the liver produces excessive glucose via glycogenolysis and gluconeogenesis, and fasting hyperglycemia begins
What are the consequences of hypersecretion of stress hormones in insulopenia?
- Impairing insulin secretion
- Antagonizing insulin action.
- Promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis
- Decreasing glucose utilization and clearance
What are the consequences of hypersecretion of stress hormones in insulopenia?
- Impairing insulin secretion
- Antagonizing insulin action.
- Promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis
- Decreasing glucose utilization and clearance
Effects of insulinopaenia - lipolysis?
insulin deficiency + elevated counter-regulatory hormones > Lipolysis/ Impaired lipid synthesis
= Increased lipid plasma concentrations (cholesterol, triglycerides, FFAs)
What do counter-regulatory hormones do?
cause insulin ineffectiveness during stress as counterregulatory hormones block insulin action
Effects of insulinopaenia - ketosis?
- insulin deficiency + glucagon excess
- FFAs > ketone bodies
(β-hydroxybutyrate and acetoacetate) - Metabolic acidosis and Kussmaul respiration
Note: The rate of formation of these ketone bodies exceeds the capacity for peripheral utilization and renal excretion.
What is the relevance of acetone?
Acetone, formed by nonenzymatic conversion of acetoacetate, is responsible for the characteristic fruity odor of the breath
Effects of insulinopaenia - impaired consciousness?
- Glucose, ketones and cation excretion in urine
- Increased losses of water and electrolyte
- Progressive dehydration
- Acidosis
- Hyperosmolality
- Diminished cerebral oxygen utilization - Impaired consciousness and coma
What are electrolyte imbalances in DKA?
- Electrolyte abnormalities occurs through a loss of electrolytes in urine and transmembrane alterations resulting from acidosis
- Depending on the duration of the DKA, serum potassium concentrations at diagnosis may be increased, normal or decreased
- But intracellular potassium concentration will be decreased
Note: A depletion of serum potassium concentration is a very serious sign of total body potassium depletion.
What are the causes of electrolyte imbalance in DKA?
- Potassium
- Intracellular potassium is exchanged for hydrogen ions
- Clearance of potassium by the kidneys (activation of the renin-angiotensin-aldosterone axis) - Phosphate
- Increased renal excretion required for excretion of excess hydrogen ions (buffer) - Sodium
- Osmotic diuresis
- Vomiting
Precipitating factors for DKA?
- Poor metabolic control or missed insulin doses
- Insulin omission and other diabetes mismanagement accounts for the majority of DKA episodes in children with established diabetes - Illness eg vomiting and dehydration
- Medications – e.g. corticosteroids
- Drugs and Alcohol
How is illness a precipitating factor?
Intercurrent illnesses, particularly when associated with vomiting and dehydration, can precipitate DKA by increasing stress hormone levels (catecholamines, cortisol, and glucagon) that increase hepatic glucose output, cause peripheral insulin resistance, and promote ketogenesis.
Which medications are precipitating factors?
corticosteroids, atypical antipsychotics, diazoxide, and high-dose thiazides, have precipitated DKA in individuals not previously diagnosed with type 1 diabetes mellitus.
How are drugs and alcohol precipitating factors?
In adolescents with type 1 diabetes, use of illicit drugs and alcohol may interfere with adherence to good medical management recommendations, resulting in poor metabolic control, which increases the risk for DKA
Who is a suspected diabetic?
polydipsia, polyuria, polyphagia, weight loss, vomiting, or abdominal pain, history of infection or inciting event
Who is a known diabetic?
The usual insulin regimen, timing and amount of last dose
Clinical presentation of DKA?
Polyuria
Polyuria in the presence of dehydration indicates osmotic diuresis and differentiates patients with DKA from patients with gastroenteritis or other gastrointestinal disorders.
Polydypsia
Nausea
Vomiting
Abdominal pain (DDx: Acute abdomen; paralytic ileus)
Tachypnoea with deep (Kussmaul) respirations
Fruity odor (acetone)
Altered level of consciousness (disorientation to coma)
Clinical presentation of DKA?
Clinical signs of intravascular volume depletion:
1. Tachycardia
2. Poor peripheral perfusion
3. Decreased skin turgor
Why do the signs of DKA tend to be less prominent than in patients with the same degree of fluid loss from other conditions?
- the intravascular volume is relatively preserved due to increased intravascular osmolality resulting from hyperglycemia
- free water losses frequently exceed sodium losses
- hyperglycemia - induced osmotic diuresis preserves urine output
Why should children with DKA be rehydrated based upon a presumed fluid deficit and clinical response rather than using clinical estimates of the degree of dehydration?
