Hypoglycemia Flashcards
(40 cards)
What is Hypoglycemia?
Hypoglycemia is defined as an abnormal decrease in plasma glucose concentrations less than 2.5mmol/L
The plasma glucose concentration at which observable symptoms of hypoglycemia appear in adult and newborns/infants is at about:
2.8–3.0 mmol/L, Newborns and infants are known to tolerate lower levels of plasma glucose without eliciting any sign of hypoglycemia.
Why is glucose required?
Glucose is an important metabolic fuel
especially brain:
- energy requirements more than twice other cell
- glucose is the normal substrrate
- cannot synthesise glucose
- cannot store more than a few minutes supply
- cannot utilise fatty acids
States of fasting include:
Fed State/Post-absorptive state
- defined as 2 hours after a meal
Fasting State
- exists after (even 10) 12 – 24 hours after the last meal
- overnight fast
Starvation State
- no food intake for greater than 48hours
Glucose absorption from the GIT ceases by_____ hours after a meal
6-8 hours after a meal
How is Euglycaemia maintained in fasting state?
Euglycaemia (normal glucose levels) is maintained by the breakdown of endogenous sources of energy: Glycogen, Triacylglycerols, Amino acids
The pancreas decreases insulin secretion and increases glucagon secretion
Epinephrine levels also increase in response to the falling glucose levels
The lack of insulin also stimulate hormone sensitive lipase on adipose cells
What occurs during Starvation?
No liver glycogen
Only source of glucose is gluconeogenesis
Ketosis becomes more prominent as fuel for the tissues including the brain
Kidney becomes gluconeogenic
Discuss Insulin
Protein hormone produced by the β-cells of the Pancreas
Produced as part of a precursor molecule pre-proinsulin
Preproinsulin - Proinsulin - Insulin and C- peptide
Insulin is secreted in equi-molar amounts with C-peptide.
Imbalance between Insulin and C-peptide can be an indication of exogenous insulin
Function of insulin in the body organs?
Brain : Increase glucose entry into by GLUT-1,3
(Not insulin requiring)
Muscle: Increases glucose entry (GLUT-4). Increases glycogen synthesis
Liver: Enhances glucose entry (via + glucokinase)
(Entry mediated by GLUT-2, not insulin dependent)
Inactivates liver glycogen phosphorylase
Stimulates glycogen synthase
Inhibits gluconeogenesis
Adipose tissue: Promotes glucose entry (by GLUT-4) mainly for glycerol synthesis
How does insulin INCREASE FAT SYNTHESIS AND STORAGE?
- Increased glucose utilization action has fat sparing effect
- Excess glucose converted to fat (when liver glycogen is 5 – 6% concentration)
- Fat synthesized is used to form TG, which is incorporated into LP and secreted
- Insulin activates lipoprotein lipase in the adipose tissue to breakdown LPs to form FAs which are absorbed
- In adipose tissue, Insulin inhibits hormone sensitive lipase
6.Increases glucose entry into cell, forms glycerol to combine with FAs to form TG
Other effects of Insulin
Promotes synthesis of protein and inhibits degradation of proteins
Interacts synergistically with GH to promote growth
Counter-regulatory Hormones
Glucagon
Epinephrine
Norepinephrine
Cortisol
Growth Hormone
Discuss glucagon
Secreted by the α-cells of the pancreas
Stimulates glycogenolysis and ↑ blood glucose conc. within minutes
Stimulates gluconeogenesis, increasing uptake of amino acids into Liver
Activates hormone sensitive lipase in adipose tissue, ↑ FFA conc.
Main counter-regulatory hormone during acute hypoglycaemia
Types of Hypoglycemia
Fasting Hypoglycemia:
Occurs in the fasting state
Non-fasting/Reactive/Postprandial hypoglycemia
Occurs only in response to a meal
Discuss Fasting Hypoglycemia With Hyperinsulinism
Insulin Therapy
Sulfonylurea Overdose (they encourage the release of endogenous insulin)
Factitious Hypoglycemia
Autoimmune Hypoglycemia
Pentamidine-Induced
Pancreatic β- cell tumours
Discuss Fasting Hypoglycemia Without Hyperinsulinism
Hepatic parenchymal damage
Severe Muscle wasting
Chronic starvation
Uremia
Adrenocortical deficiency
Inborn errors of CHO metab. e.g G6PD deficiency
Discuss Non fasting hypoglycemia
- Postgastrectomy alimentary hypoglycemia (revomal of the stomach, glucose enters directly into small intestine. insulin levels shoot up, greatly increases rate of absorption)
- Post gastric bypass hypoglycemia
- Functional alimentary hypoglycemia
- Pancreatic-islet hyperplasia
- Late hypoglycaemia (Occult diabetes)
How does insulin therapt cause hypogycemia?
Insulin treated diabetics are bulk of patients with hypoglycemia
Advent of intensive glycemic control
Several episodes per week
About 2- 4 % deaths associated with hypoglycemia
What are the risk factors of fasting hypoglycemia?
Hypoglycaemia unawareness
Insulin doses are excessive, ill timed or wrong type
Influx of exogenous glucose is reduced (fast or missed meals)
Insulin dependent glucose utilisation is increased
Insulin sensitivity is increased
Endogenous glucose production is reduced (alcohol ingestion)
Insulin clearance is reduced (renal failure)
Sulfonylurea overdose in association with hypoglycemia?
Associated with agents with prolonged half life (chlorpropamide,35hrs)
Also older patients with impaired hepatic or renal function
Factitious hypoglycemia
Self induced hypoglycemia (with insulin or sulfonylurea)
Common in health professionals, diabetics or their relatives
Call for attention, psychiatric disturbances
Also patient error, or pharmacist prescription mishap
Pancreatic β-cell tumours (Insulinomas)
Commonest cause in an otherwise healthy adult
Most are benign and single
May be familial (MEN 1)
Hepatic parenchymal disease
Reduced hepatic gluconeogenesis
Fulminant viral hepatitis or toxic damage
