hypoglycaemia Flashcards
1
Q
what is hypoglycaemia? 3
A
- Defined as a blood glycose level of below mM (72mg/dL)
- Symptoms may develop at higher levels if there is rapid fall of previously elevated levels, although some individuals may show no effects even below 4mM
- A rapid fall in blood glucose may produce a phase of sweating, tachycardia and agitation due to activation of the sympathetic nervous system and release of adrenaline and glucagon
2
Q
what are the signs and symptoms of hypoglycaemia? 4
A
- Equivalent to anoxia and may include moodiness, faintness, numbness in arms and hands, blurred vision, confusion, memory loss, dizziness or lethargy that may progress to coma
- Serious consequences relate to effects on the brain- loss of cognitive function, seizures and coma
- Loss of consciousness occurs at blood glucose levels of 2.5mM (45mg/dL)
- Rapid restoration of blood glucose (by i.v or injection of glucagon) is essential and prolonged or repeated hypoglycaemia ay result in permanent brain damage
3
Q
what are the causes of hypoglycaemia? 8
A
- Exercise
- Fasting
- Excess exogenous insulin
- Insulinoma: excess of endogenous insulin
- Inhibition of endogenous glucose production
- Hypernatremia (diabetes insipidus)
- Hypovolaemia from vomiting, dehydration
- Pathologies such as adrenal insufficiency
4
Q
describe alcohol induced hypoglycaemia? 4
A
- Develops several hours after alcohol ingestion
- Occurs on depletion of glycogen stores when blood glucose is reliant on hepatic gluconeogenesis
- In the short term (24 hours); consumption of alcohol places additional stresses on gluconeogenesis as alcohol is metabolized primarily in the liver by an unregulated process
- In the long term (years): gluconeogenesis may also be decreased by liver damage and reduced muscle mass (longer term)
5
Q
describe the metabolism of alcohol? 4
A
- ethanol is rapidly metabolised by the enzyme alcohol dehydrogenase in the liver to acetaldehyde
- the reaction requires NAD+ as a co-enzyme results in a high NADH:NAD+ ratio in the cytosol
- acetaldehyde produced is transported into the mitochondria where it is oxidised to acetate by acetaldehyde dehydrogenase
- this results in a high NADH: NAD+ ratio in the mitochondria
6
Q
what are the metabolic consequences of alcohol? 2
A
- ethanol metabolism in the liver increases to NADH + H+ and shifts the equilibrium of the reactions
- this reduces the availability of substrates for entry into gluconeogenesis to maintain plasma glucose levels (pyruvate and oxaloacatate to lactate and malate)
7
Q
what are the symptoms of alcohol-induced hypoglycaemia? 3
A
- occurs as a result of ethanol ingestion when blood glucose levels are reliant on gluconeogenesis (12-24 hours after a meal when glycogen stores are depleted)
- fall in blood glucose leads to a stress response (rapid heartbeat, clammy skin) in an effort to enhance the stimulation of gluconeogenesis by combined action of glucagon and adrenaline
- rapid breathing is a physiologic response to metabolic acidosis, resulting from excess of lactic acid
8
Q
what are the effects on lipid metabolism of long term alcohol consumption? 6
A
- 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, and can also be exported as VLDL
- fatty liver disease can progress over time in 3 stages:
- the liver becomes inflamed causing damage to the liver tissue (also known as steatohepatitis)
- scar tissue forms at sites of damage (known as fibrosis)
- extensive sacrifice tissue replaces healthy tissue (known as cirrhosis of the liver)
9
Q
what are the effects on efficiency of ethanol metabolism due to long term alcohol consumption? 2
A
- acetate produced fro EtOH can be converted into acetyl-CoA
- further processing of acetyl-CoA in the TCA cycle is prevented because high levels of NADH inhibits both citrate synthase and alpha- ketoglutarate dehydrogenase
10
Q
what are the consequences of the accumulation of acetyl CoA? 2
A
- the production of ketone bodies which are released into the blood and exacerbates the already acidic conditions resulting from high acetate levels
- processing of acetate in the liver becomes insufficient, leading to the build-up of acetaldehyde which is highly toxic
11
Q
describe alcohol induce hepatomegaly? 3
A
- alcohol consumption decreases the activity of the proteasome
- this leads to the accumulation of protein, which causes the enlargement of the liver
- decreased proteasome activity also increases oxidative stress
12
Q
describe alcohol induced thiamine (B1) deficiency? 4
A
- people with chronic alcoholism often have deficient intakes of micronutrients and minerals
- 50% of alcoholics with liver disease will have a thiamine deficiency
- symptoms include anorexia, irritability and bad short-term memory
- this can be caused by malnourishment, ethanol interfering with the GI absorption, hepatic dysfunction which hinders storage and activation of thiamine pyrophosphate
13
Q
what is thiamine? 2
A
- cofactors for many enzymes such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase
- has a half-life of around 10-20 days, deficiency can occur rapidly after depletion
14
Q
what are glycogen storage diseases? 5
A
- inherited diseases in which the stores of glycogen are affected by defects in either the enzymes of synthesis or degradation of glycogen
- any different types depend on which enzymes is affected
- they are all autosomal recessive except for type IX which is sex-linked
- they all result in the production of an abnormal amount of abnormal type of glycogen
- they are a family of inborn errors of metabolism with an overall frequency of 1:20,000 to 1:40,000 births
15
Q
what are the different types of glycogen storage disease and the enzyme they affect? 5
A
- type 0- glycogen synthase
- type 1- G-6-Pase
- type III- debranching enzymes
- type IV- branching enzyme
- type V- glycogen phosphorylase
