hypoglycaemia Flashcards
what is hypoglycaemia?
when blood glucose falls below 4mM
why does a rapid fall in blood glucose cause sweating, tachycardia and agitation?
due to activation of the sympathetic nervous system and release of adrenaline and glucagon
what are the symptoms of hypoglycaemia?
- moodiness
- faintness
- numbness in arms and hands
- blurred vision
- confusion
- memory loss
- dizziness
- lethargy
what are the serious consequences of hypoglycaemia?
relate to the brain:
- loss of cognitive function
- seizures
- coma
when does loss of conciseness occur with hypoglycaemia?
when blood glucose reaches 2.5mM
what are the causes of hypoglycaemia?
- fasting or exercise
- hypernatraemia
- hypovolaemia from vomiting, dehydration…
- pathologies such as adrenal insufficiency
when does alcohol-induced hypoglycaemia occur?
- several hours after alcohol ingestion
- occurs on depletion of glycogen stores when blood glucose is reliant on hepatic gluconeogenesis
what happens in the short term with alcohol-induced hypoglycaemia?
consumption of alcohol places additional stresses on gluconeogenesis as alcohol is metabolised primarily in the liver by an unregulated process
what happens in the long term with alcohol-induced hypoglycaemia?
gluconeogenesis may also be decreased by liver damage and reduces muscle mass
what metabolises ethanol in the liver?
alcohol dehydrogenase
what is required for metabolism of ethanol in the liver?
NAD+ as a co-enzyme
what is the end result of ethanol metabolism in the liver?
a high NADH:NAD+ ratio in the cytosol
where is acetaldehyde transported to?
the mitochondria
what is acetaldehyde oxidises to and by?
oxidised to: acetate
oxidised by: acetaldehyde dehydrogenase
what does the oxidation of acetaldehyde result in?
high NADH:NAD+ ratio in the mitochondria
what is the metabolic consequence of alcohol metabolism?
reduces the availability of substrates for entry into gluconeogenesis to maintain plasma glucose levels
when do symptoms of alcohol-induced hypoglycaemia show?
occurs as a result of ethanol ingestion when blood glucose levels are reliant on gluconeogenesis
what are the symptoms of alcohol-induced hypoglycaemia?
- fall in blood glucose leads to stress response, in an effort to enhance the stimulation of gluconeogenesis by combined action of glucagon and adrenaline
- rapid breathing is a physiological response to metabolic acidosis resulting from excess lactic acid
what is the effect on lipid metabolism of long term alcohol consumption?
- high levels of NADH inhibit fatty acid oxidation: instead the excess NADH signals that conditions are right for fatty acid synthesis
- TGs accumulate in the liver causing a condition known as ‘fatty liver’ - also exported as VLDL
what are the 3 stages of fatty liver disease progression?
1) the liver becomes inflamed causing damage to the liver tissue (steatohepatits)
2) scar tissue forms at site of damage (fibrosis)
3) extensive scar tissue replaces healthy tissue (cirrhosis_
what is acetate produced from EtOH converted to?
acetyl-CoA
what is the effect on efficiency of ethanol metabolism with long term alcohol consumption?
further processing of acetyl-CoA in TCA cycle prevented because high levels of NADH inhibits both citrate synthase and alpha-ketoglutarate dehydrogenase
what are the 2 consequences of accumulation of acetyl-CoA?
1) production of ketone bodies which are released into the blood and exacerbates the already acidic conditions resulting from high lactate levels
2) processing of acetate in the liver becomes inefficient, leading to a build up of acetaldehyde, which is highly toxic
how does alcohol incited hepatomegaly occur?
- alcohol consumption decreases the activity of the proteosome
- leads to accumulation of protein, which causes enlargement of the liver
- decreased proteasome activity also increases oxidative stress
