DKA

Question 1

What is DKA?

Answer 1

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

Question 2

What is the cause of DKA?

Answer 2

is caused by absolute or relative insulin deficiency

Question 3

Epidemiology of DKA?

Answer 3

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

Question 4

Definition of DKA?

Answer 4

hyperglycemia + metabolic acidosis + ketosis

Question 5

Hyperglycemia?

Answer 5

Blood glucose of >200 mg/dL (11 mmol/L)

Question 6

Metabolic acidosis?

Answer 6

1. a venous pH <7.3
   or
2. plasma bicarbonate <15 mEq/L (15 mmol/L)

Question 7

Ketosis?

Answer 7

Determined by the presence of ketones in the blood or urine
>3 mmol

Question 8

Problems with measuring ketosis?

Answer 8

Standard qualitative measurements of ketones (as acetoacetate) can underestimate severity of ketosis

Question 9

How to accurately measure ketosis?

Answer 9

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

Question 10

What is the fasted state?

Answer 10

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

Question 11

What is a catabolic state?

Answer 11

breaking down or losing overall mass, both fat and muscle

Question 12

What is a postprandial state?

Answer 12

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

Question 13

What is an anabolic state?

Answer 13

where the body builds and repairs muscle tissue

Question 14

What is T1 diabetes mellitus?

Answer 14

is a progressive low-insulin catabolic state in which feeding does not reverse but rather exaggerates these catabolic processes

Question 15

Influence of high plasma insulin (postprandial state) on the liver?

Answer 15

1. glucose uptake
2. glycogen synthesis
3. lipogenesis
4. absence of gluconeogenesis
5. absence of ketogenesis

Question 16

Influence of low plasma insulin (fasted state) on the liver?

Answer 16

1. glucose production
2. glycogenolysis
3. absence of lipogenesis
4. gluconeogenesis
5. ketogenesis

Question 17

Influence of high plasma insulin on muscle?

Answer 17

1. glucose uptake
2. glucose oxidation
3. glycogen synthesis
4. protein synthesis

Question 18

Influence of low plasma influence on the muscle?

Answer 18

1. absence of glucose uptake
2. fatty acid and ketone oxidation
3. glycogenolysis
4. proteolysis and amino acid release

Question 19

Influence of high plasma insulin on adipose tissue?

Answer 19

1. glucose uptake
2. lipid synthesis
3. triglyceride uptake

Question 20

Influence of low plasma insulin in adipose tissue?

Answer 20

1. absence of glucose uptake
2. lipolysis and fatty acid release
3. absence of triglyceride uptake

Question 21

Effects of insulopenia - hyperglycemia?

Answer 21

1. hyperglycemia
2. Osmotic diuresis (> 180mg/dL; 10mmol/L)
   - loss of calories and electrolytes
   - persistent dehydration
3. Hypersecretion of stress hormones (epinephrine, cortisol, growth hormone, and glucagon)

Question 22

How does insulopaenia cause hyperglycemia?

Answer 22

• glucose utilization by muscle and fat decreases and postprandial hyperglycemia appears
• the liver produces excessive glucose via glycogenolysis and gluconeogenesis, and fasting hyperglycemia begins

Question 23

What are the consequences of hypersecretion of stress hormones in insulopenia?

Answer 23

1. Impairing insulin secretion
2. Antagonizing insulin action.
3. Promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis
4. Decreasing glucose utilization and clearance

Question 24

What are the consequences of hypersecretion of stress hormones in insulopenia?

Answer 24

1. Impairing insulin secretion
2. Antagonizing insulin action.
3. Promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis
4. Decreasing glucose utilization and clearance

Question 25

Effects of insulinopaenia - lipolysis?

Answer 25

insulin deficiency + elevated counter-regulatory hormones > Lipolysis/ Impaired lipid synthesis = Increased lipid plasma concentrations (cholesterol, triglycerides, FFAs)

Question 26

What do counter-regulatory hormones do?

Answer 26

cause insulin ineffectiveness during stress as counterregulatory hormones block insulin action

Question 27

Effects of insulinopaenia - ketosis?

Answer 27

1. insulin deficiency + glucagon excess 2. FFAs > ketone bodies (β-hydroxybutyrate and acetoacetate) 3. Metabolic acidosis and Kussmaul respiration Note: The rate of formation of these ketone bodies exceeds the capacity for peripheral utilization and renal excretion.

Question 28

What is the relevance of acetone?

Answer 28

Acetone, formed by nonenzymatic conversion of acetoacetate, is responsible for the characteristic fruity odor of the breath

Question 29

Effects of insulinopaenia - impaired consciousness?

Answer 29

1. Glucose, ketones and cation excretion in urine 2. Increased losses of water and electrolyte - Progressive dehydration - Acidosis - Hyperosmolality - Diminished cerebral oxygen utilization 3. Impaired consciousness and coma

Question 30

What are electrolyte imbalances in DKA?

Answer 30

- 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.

Question 31

What are the causes of electrolyte imbalance in DKA?

Answer 31

1. Potassium - Intracellular potassium is exchanged for hydrogen ions - Clearance of potassium by the kidneys (activation of the renin-angiotensin-aldosterone axis) 2. Phosphate - Increased renal excretion required for excretion of excess hydrogen ions (buffer) 3. Sodium - Osmotic diuresis - Vomiting

Question 32

Precipitating factors for DKA?

Answer 32

1. 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 2. Illness eg vomiting and dehydration 3. Medications – e.g. corticosteroids 4. Drugs and Alcohol

Question 33

How is illness a precipitating factor?

Answer 33

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.

Question 34

Which medications are precipitating factors?

Answer 34

corticosteroids, atypical antipsychotics, diazoxide, and high-dose thiazides, have precipitated DKA in individuals not previously diagnosed with type 1 diabetes mellitus.

Question 35

How are drugs and alcohol precipitating factors?

Answer 35

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

Question 36

Who is a suspected diabetic?

Answer 36

polydipsia, polyuria, polyphagia, weight loss, vomiting, or abdominal pain, history of infection or inciting event

Question 37

Who is a known diabetic?

Answer 37

The usual insulin regimen, timing and amount of last dose

Question 38

Clinical presentation of DKA?

Answer 38

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)

Question 39

Clinical presentation of DKA?

Answer 39

Clinical signs of intravascular volume depletion: 1. Tachycardia 2. Poor peripheral perfusion 3. Decreased skin turgor

Question 40

Why do the signs of DKA tend to be less prominent than in patients with the same degree of fluid loss from other conditions?

Answer 40

1. the intravascular volume is relatively preserved due to increased intravascular osmolality resulting from hyperglycemia 2. free water losses frequently exceed sodium losses 3. hyperglycemia - induced osmotic diuresis preserves urine output

Question 41

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?