Hypoglycaemia L11 Flashcards
Hypoglycaemia definition
Blood glucose level below 4mM
Symptoms may develop at higher levels if there’s a rapid fall of previously elevated levels, although some individuals may show no effect even below 4mM
Rapid fall in glucose causes what
Phase of sweating, tachycardia and agitation due to release of adrenaline
Hypoglycaemia symptoms
Equivalent to cerebral anoxia and may include
- moodiness
- faintness
- numbness in arms and hands
- blurred vision
- dizziness
- lethargy that may progress to coma
Serious consequences of hypoglycaemia
Relate to effects on the brain
Loss of cognitive function, seizures and coma
Causes of hypoglycaemia
May be due to fasting or exercise
Other causes
- hypernatraemia
- hypovolaemia from vomiting, dehydration
- ingestion of alcohols
- pathologies such as adrenal insufficiency
Alcohol induced hypoglycaemia
Develops several hours after alcohol ingestion
Occurs on depletion of glycogen stores when blood glucose is reliant on hepatic gluconeogenesis
Consumption places additional stresses on gluconeogenesis, as alcohol is metabolised primarily in the liver by an unregulated process
Gluconeogenesis may also be decreased by liver damage and reduced muscle mass
Mechanisms of alcohol induced hypoglycaemia
Ethanol rapidly metabolised by the enzyme alcohol dehydrogenase in the liver
C2H5OH –(AD)–> CH3CHO
Reaction requires NAD+ as co-enzyme
Results in high NADH:NAD+ rate in cytosol
Acetaldehyde produced is transported into the mitochondria where it is oxidised to acetate by acetaldehyde dehydrogenase
CH3CHO –(AlD)–> CH3COOH
Results in high NADH:NAD+ ratio in the mitochondria
Other biochemical consequences of 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
Acetate produced from EtOH can be converted into acetyl-CoA
Further processing of acetyl-CoA in TCA cycle prevented because high levels of NADH inhibit both isocitrate dehydrogenase and a-ketoglutarate dehydrogenase
Accumulation of acetyl CoA has two consequences
- Production of ketone bodies which are released into the blood
Exacerbates the already acidic conditions resulting from high lactate levels - Processing of acetate in the liver becomes inefficient leading to build up of acetaldehyde
Acetaldehyde
The immediate end product of alcohol metabolism
Highly toxic
Hepatomegaly
Alcohol consumption decreases the activity of the protesome
Leads to accumulation of protein, which causes enlargement of the liver
Decreased proteosome activity also increases oxidative stress
Thiamine deficiency
Chronic alcoholics frequently have deficient intakes of micronutrients and minerals
50% of alcoholics with liver disease will have thiamine deficiency (B1)
Thiamine deficiency will cause
Malnourishment
Ethanol interferes with GI absorption
Hepatic dysfunction, which hinders storage and activation to thiamine pyrophosphate
Thiamine as a cofactor for many enzymes
Half life of 10-20 days, deficiency can occur rapidly during depletion
Coenzyme in central energy yielding pathways
Glycogen storage disease
Inherited disease in which the stores of glycogen are affected by defects in either the enzymes of synthesis or degradation glycogen
10 different types depending on which enzyme is affected
All autosomal recessive except for type IX which is sex-linked
All result in the production of an abnormal amount or abnormal type of glycogen
Frequency of glycogen storage diseases
1:20000-1:43000 births
Type 0
Glycogen synthase
Type I
G-6-Pase
Type III
Debranching enzyme
Type IV
Branching enzyme
Type V
Glycogen phosphorylase
Type I. von Gierke’s disease
Affects mainly liver and kidneys caused by defiency in glucose-6-phospatase
Excess glucose-6-phosphate and consequent storage of excess glycogen and liver enlargement; and inability to release glucose during fasting leads to hypoglycaemia
Type II. Pompe’s disease
A deficiency of a-1,4 glucosidase activity in the lysosome
Can be one of the most devastating of the glycogen storage diseases
Causes death by cardiorespiratory ailure
Type III Cori’s disease
The amylo 1,6 glucosidase (de-branching enzyme) is deficient
Unable to break down glycogen
Resulting in hypoglycaemia
Strangely, symptoms often disappear at puberty
Type IV Andersen’s disease
One of the most severe of these diseases
Liver glycogen in normal amounts by comprises long unbranched chains that have low solubility
Sufferers seldom live beyond four years
Type V. McArdle’s syndrome
Affects muscle glycogen phosphorylase (liver enzyme is normal)
Muscle cannot break down glycogen (which accumulates)
Sufferers have low tolerance to exercise and fatigue easily
Painful muscle cramps after exercise
Otherwise have normal life-span
Von Gierke’s disease symptoms
Enlarged livers and/or kidneys
Stunted growth
Severe tendencies to hypoglycaemia, hyperlactaemia and hyperlipidaemia
May also show hyperuricaemia and neutropaenia
Symptoms appear when intervals between feeds increases and the infant sleeps through the night or when an illness prevents normal feeding routine
