Hypoglycaemia Flashcards
Hypoglycaemia definition
Blood glucose level below 4 mM (72 mg/dL)
Effects of a rapid fall in blood glucose level
The release of adrenaline causes the following symptoms:
- Sweating
- Tachycardia
- Agitation
Symptoms of hypoglycaemia
Moodiness
Faintness
Numbness in arms and hands
Blurred vision
Dizziness
Lethargy
Symptoms are similar to cerebral anoxia as the brain is affected massively.
Loss of consciousness happens when Bgl are 2.5mmol/L and below
If not resolved, can lead to permanent brain damage
Causes of hypoglycaemia
Fasting
Exercise
Hypernatraemia
Hypovolumia
Alcohol
Adrenal insufficiency pathology
Alcohol-induced hypoglycaemia
Alcohol inhibits hepatic gluconeogenesis.
Alcohol metabolism causes an increase in NADH in the cytosol and mitochondria.
High NADH:NAD+ ratio shifts equilibrium in glycolytic reactions:
- Increases Lactate from pyruvate
- Increases malate from OAA
- Increase G3P from DHAP
DHAP, OAA and pyruvate cannot drive gluconeogenesis anymore
Alcohol metabolism in the liver
- Ethanol—-> acetaldehyde
- Uses alcohol dehydrogenase
- Reduces NAD+ to NADH
- Occurs in cytosol - Acetaldehyde —-> Acetate/ Acetic acid
- Uses aldehyde dehydrogenase
- Reduces NAD+ to NADH
- Occurs in mitochondria
Both processes increases NADH:NAD+ ratio in the cytosol and mitochondria of hepatocytes
Reactions of the equilibrium shifted by alcohol [3]
Pyruvate + NADH +H+——–> Lactate + NAD+
OAA + NADH + H+ ——> Malate + NAD+
DHAP + NADH + H+ —–> G-3P + NAD+
Hormonal response to hypoglycaemia
Release of adrenaline and glucagon:
- Increased heart rate
- Clammy skin
- Rapid breathing, due to metabolic acidosis [lactic acid build up]
Alcohol on fat metabolism
Ethanol metabolism = increased NADH
- Inhibits fatty acid oxidation and stimulates fatty acid synthesis
This accumulates TGs and can lead to fatty liver.
Acetyl CoA build up from acetate due to high levels of NADH.
- Isocitrate and alpha-ketoglutarate DH inhibited
Accumulation of acetyl CoA in alcohol metabolism
Caused from acetate build up in ethanol metabolism.
Increased ketosis—> exacerbates already acidic conditions caused by lactate.
Acetate processing becomes inefficient and causes acetaldehyde build-up.
- High toxic.
Alcoholic hepatomegaly
Ethanol processing decreases proteosome activity [degrade unneeded or damaged proteins]:
- Increases accumulation of proteins in the liver = enlargment
- Increases oxidative stress
Alcoholics and thiamine deficiency
Chronic alcoholics have deficiencies with intake of micronutrients due to:
- Malnourishment
- Interfered GI absorption
- Hepatic dysfunction due
Thiamine deficiency- B1 deficiency
- Hepatic damage hinders storage and activation of thiamine pyrophosphate
Thiamine as a co-factor
Co-factor for:
- Pyruvate DH
- Alpha-ketoglutarate DH
- Transketolase
Glycogen storage disease Type I
Von Gierke’s disease
Deficiency in G-6-Pase
- Inability to release glucose during fasting
G-6-P cannot be converted to glucose so there is XS glycogen = liver enlargement
Increases conversion of FA to TG and VLDL in the liver = fatty liver and hyperlipidemia
- hepatoma
- accumulation of fat in cheeks and bum
Glycogen storage disease Type II
Pompe’s disease
- Autosomal recessive
Deficiency in alpha 1-4 glucosidase in lysosomes.
- Glycogen cannot be broken down.
- Accumulation of glycogen in lysosomes
Causes death by cardiorespiratory failure- weakness in skeletal and cardiac muscle
