Investigation of hypoglycaemia Flashcards
What are signs and symptoms of Hypoglycaemia?
Activation of autonomic nervous system
- Adrenergic responses e.g. palpitations, tremor, anxiety
- Cholinergic responses e.g. sweating, hunger
Neuroglycopenia
- Confusion, coma, seizures
What is the definition of hypoglycaemia?
- Glucose concentration low enough to cause symptoms/ signs of impaired brain function
- Whipple’s triad in adults: signs/ symptoms, documented low glucose, administration of glucose relieves symptoms
Why is hypoglycaemia hard to define in infants?
In infants/ young children, it is difficult to reliably recognise/ communicate symptoms. Not possible to identify a single plasma glucose concentration below which brain injury occurs
- Altered by presence of alternative fuels such as ketones
- Extent of injury influenced by duration and degree of hypoglycaemia
- Analytical variation in glucose concentration
What is the figure used to define hypoglycaemia?
Hypoglycaemia often defined as plasma glucose <2.6 mmol/L
What is the effect of insulin on metabolism?
- Increase glucose uptake
- Decrease lipolysis
- Deceased ketogenesis
- Decrease gluconeogenesis
- Decreased glycogenolysis
Counter-regulatory hormones such as glucagon, adrenaline, cortisol, growth hormone acts in reverse to the effects below
How does Hypoglycaemia occur in Neonates?
- In the first hours after birth: hepatic glycogen breakdown. Capable of gluconeogenesis 4-6 hours of age
- Transient low blood glucose common in first 12 hours of life
- Greater risk of hypoglycaemia as larger relative brain size and comparatively small muscle mass
- Full biochemical screening unrequired unless not responding to feed
What are indications for neonatal glucose monitoring?
- Preterm (<37 weeks gestation): Less adipose tissues, less glycogen stores as it occurs in the 3rd trimester
- Low birth weight (<2.5kg)
- Large for dates (>4.5kg): Large insulin but not a large supply of glucose anymore
- Maternal diabetes mellitus
- Infection or other illness
- Poor condition at birth
- Maternal use of β blockers (e.g. Labetolol)
What is the Pathogenesis of hypoglycaemia in Paediatrics?
- Increased glucose utilisation
- Impaired glycogen metabolism
- Impaired ketogenesis and ketone body utilisation
- Reduced gluconeogenesis
- Interference with glucose homeostasis secondary to a disturbance of intermediary metabolism
- Other causes and associations
- Drug-related
- Idiopathic ketotic hypoglycaemia
What are causes of increased glucose utilisation?
- Hyperinsulinaemic hypoglycaemia
- Stress e.g. hypoxia, respiratory distress, hypothermia
What are causes of Hyperinsulinaemia Hypoglycaemia?
- Congenital hyperinsulinism (CHI): mutations in ABCC8, KCNJ11, GLUD1, GCK, HADH, HNF4A
- Secondary Causes (usually transient): Maternal Diabetes Mellitus, Intrauterine Growth Retardation, Perinatal Asphyxia, Rhesus Isoimmunisation.
- Other syndromes: Beckwith-Wiedemann, Soto
- Insulinoma
How is insulin secreted?
- ATP sensitive potassium channel made up by Kir 6.2 and SUR-1. These channels are involved in the channelopathies
- Potassium sensitive channel is usually open and calcium channel is usually closed
- Glucose enters the cell through the GLUT2 and is phosphorylated by the glucokinase. Increase in ATP/ADP ratio which causes the potassium sensitive channel to close.
- Leads to depolarisation of the membrane and influx of calcium ions through voltage gated channels. The rise in intracellular calcium causes secretion of insulin.
How does Diazoxide work?
If the channels are dysfunctional, the potassium channel remains closed and therefore the Diazoxide binds the SUR-1 to keep the channel open and stop depolarisation.
What are examples of impaired glycogen metabolism?
Impaired Glycogen Synthesis
- Glycogen synthase deficiency (GSD 0): Uncommon cause of fasting ketotic hypoglycaemia
Impaired Glycogenolysis
- Hepatic glycogen storage disorders: I, III, VI, IX
What are causes of impaired ketogenesis and ketone body utilisation?
- Disorders of carnitine transport
- Fatty acid oxidation defects
- Mitochondrial respiratory chain disorders
What are are some causes of reduced gluconeogensis?
Defects of gluconeogenesis (enzyme deficiency)
- Fructose 1,6 bisphosphatase deficiency
- Phosphoenolpyruvate carboxykinase deficiency
- Pyruvate carboxylase deficiency
Endocrine (failure of counter-regulatory response)
- Cortisol deficiency (hypopituitarism/ adrenal insufficiency)
- Growth hormone deficiency (isolated/ panhypopituitarism
