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
what deficiency do 50% of alcoholics with liver disease suffer with?
thiamine deficiency (B1)
what are the symptoms of thiamine deficiency?
- anorexia
- irritability
- difficulties with short term memory
what are the causes of thiamine deficiency?
- malnourishment
- ethanol interferes with GI absorption
- hepatic dysfunction which hinders storage and activation to thiamine pyrophosphate
what is the half life of thiamine?
10-20 days
what are glycogen storage diseases?
- inherited disease in which the stores of glycogen are affected by defects in either the enzymes of synthesis or degradation of glycogen
what type of disease are most glycogen storage diseases?
autosomal recessive
what type of disease is glycogen storage IX disease?
sex-linked
what do glycogen storage diseases result in??
production of abnormal amount or abnormal type of glycogen
what is type 1 Von Gierke’s disease?
deficiency of glucose-6-phosphate in liver, kidneys and intestine
what is type II Pompe’s disease?
deficiency of alpha-1,4 glucosidase activity in the lysosomes
how does type II Pompe’s disease cause death?
by cardio respiratory failure
what is type III Cori’s disease?
the amylo 1,6 glucosidase is deficient
how does type III Cori’s disease work?
unable to break down glycogen resulting in hypoglycaemia
what is type IV Andersen’s disease?
liver glycogen is in normal amounts but compromises long unbranched chains that have low solubility
what is type V McArdle’s syndrome?
- affects muscle glycogen phosphorylase
- muscle cannot breakdown glycogen
what to patients who have type V McArdle’s syndrome suffer with?
sufferers have a low tolerance to exercise and fatigue easily, with painful muscle cramps after exercise
what is the equation for the breakdown of glucose-6-phosphate?
G-6-P ——-> glucose + Pi
what is the most common GSD?
Von Gierke’s disease (25%)
what happens with Von Gierke’s disease?
- catalyses the terminal reaction of glycogenolysis and gluconeogenesis
- results in impaired export of glucose from liver from 2 pathways between meals
- causes hypoglycaemia that doesn’t response to glucagon
when do symptoms appear with Von Gierke’s disease?
when intervals between feeds increases and infants sleep through the night, or when illness prevents normal feeing routine
what are the results of Von Gierke’s disease?
- abnormal levels of glycogen accumulation in the liver and kidney: causing enlargement of the liver and kidneys
- increased glycolysis leading to lactic acidosis
- increased fatty acid, TG and VLDL synthesis and excretion
what happens with the metabolism in Von Gierke’s disease?
- body attempts to compensate for hypoglycaemia by releasing glucagon and adrenaline resulting in mobilisation of fat stores and release of fatty acids
- conversion of fatty acids to TGs and VLDL in the liver resulting in accumulation of fat in liver and hyperlipidaemia
what are the signs and symptoms of Von Gierke’s disease?
- hepatomas
- accumulation of fat in cheeks and buttocks
- enlarged livers and/or kidneys
- stunted growth
- severe tendencies to hyperglycaemia, hyperlactaemia and hyperlipidaemia
- hyperuricaemia
how does hyperuricaemia occur in Von Gierke’s disease?
as a result of hyperlactaemia as lactic acid in the blood competes for the kidney transport mechanisms
what are the management strategies and treatment of Von Gierke’s disease?
- try to correct hypoglycaemia and maintain normoglycaemia
- young infants can be fed glucose through nasogastric tubes whilst older children are fed glucose drinks at 2-3 hour intervals night and day to prevent fall in blood glucose and cerebral damage
- uncooked cornstarch may be used to prolong period between feeds
- restrict dietary lipids
- liver transplant
