2006B16 Describe the physiological consequences of acute hypoglycaemia.
List:
· Intro and importance
· Metabolic pathways and key enzymes
· Physiological response to ↓BGL
· Clinical signs of ↓BGL
Intro and importance:
· Blood glucose level tightly controlled, normally 3-7mM
· Hypoglyaemia <3mM. Symptoms and signs concealed by anaesthesia.
· Brain, RBC are reliant on glucose (brain can adapt to ketones but slowly)
· Severe hypoglycaemia can be fatal
Metabolic pathways and key enzymes:
|
Glycolysis (GL) |
· Hexokinase |
|
Gluconeogenesis (GNG) |
· From pyruvate, lactate, fructose, amino acids, glycerol · Note glucose 6 phosphatase mainly expressed in liver > renal cortex |
|
Glycogenolysis (GGL) |
· Glycogen phosphorylase |
|
Glycogenesis (GG) |
· Glycogen synthase |
|
Lipolysis (LL) |
· Hormone-sensitive lipase |
|
De novo lipogenesis (DNL) |
· Lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase |
|
Ketogenesis (KG) |
· Acetyl-CoA thiolase |
Physiological effects of hypoglycaemia:
|
Endocrine |
· ↓Insulin and ↑glucagon · ↑Cortisol (anterior pituitary -> adrenal cortex) · ↑Growth hormone (anterior pituitary) · ↑Catecholamines (adrenal medulla) |
|
Liver |
· ↑GNG, ↓GL · ↑GGL, ↓GG · ↑LL, ↓DNL |
|
Skeletal muscle |
· ↓GL · ↑GGL, ↓GGL · No direct GNG (lacks glucose 6 phosphatase) · ↑Proteolysis -> hepatic GNG via Cori cycle and glucose-alanine cycle
|
|
Adipose |
· ↓Glucose uptake for glycerol · ↑LL, ↓DNL |
Clinical signs:
|
Of hypoglycaemia |
· Weakness, hunger, agitation · Confusion, coma, death |
|
Of sympathetic hyperactivity |
· CVS: ↑HR (β1), ↑BP (CO: β1, TPR: α1) · Musculoskeletal: tremor (β2) · Skin: sweating (mAChR), pallor (α1) · Eyes: pupil dilatation (α1) |