T2 L13: Hypoglycaemia Flashcards
What is hypoglycaemia defined as?
Blood glucose below 4mM
What causes sweating, tachycardia, and agitation?
The activation of the sympathetic nervous system and release of adrenaline and glucagon
At what [blood glucose] does a person loose consciousness?
2.5 mM
How does alcohol cause hypoglycaemia?
It puts stress on gluconeogenesis as metabolism of alcohol is an unregulated process
Which enzyme matabolises ethanol?
Alcohol dehydrogenase but the reaction requires NAD+ as a co-enzyme
How is a high NADH:NAD+ ratio achieved in the mitochondria of hepatocytes during alcohol metabolism?
The enzyme alcohol dehydrogenase used to metabolise alcohol uses NAD+ as a co-enzyme so a lot of NADH is produced as a result
Which enzyme oxidises acetyl aldehyde into acetate?
Aldehyde dehydrogenase
What is the metabolic significance of NADH being oxidised for alcohol metaolism?
It means there are less substrates for gluconeogenesis
When does alcohol-induced hypoglycaemia develop?
When someone ingests ethanol while their body is reliant on gluconeogenesis
What is the mechanism behind alcoholic fatty liver?
High levels of NADH in the liver inhibit fatty acid oxidation. The NADH signals stimulate fatty acid synthesis causing an accumulation of triglycerides
What are the 3 stages of fatty liver disease progression?
- Steatohepatitis (The liver becomes inflamed and causes damage)
- Fibrosis occurs
- Cirrhosis
What are the 2 consequences of acetyl-CoA accumulation caused by alcohol consumption?
- Production of ketone bodies which exacerbate acidosis
2. Processing of acetate in the liver becomes insufficient so there is a buildup of acetylaldehyde
What is the protein mechanism behind alcoholic hepatomegaly?
Alcohol decreases activity of proteasomes leading to accumulation of proteins and therefore enlargement of the liver.
What causes nutritional deficiencies in alcoholics?
Malnourishment, Ethanol interferes GI absorption, hepatic dysfunction
What is the half-life of thiamine?
10-20 days
What % of alcoholics will have a vitamin B1 (Thiamine) deficiency?
50%
What effect do glycogen storage diseases have on glycogen?
Abnormal amount or abnormal type of glycogen are produced
What is Type 1 (Von Gierke’s disease)?
A deficiency of glucose-6-phosphate resulting in high G-6-P in liver and kidneys and impaired export of glucose from the liver. Causes hypoglycaemia that doesn’t respond to glucagon. Symptoms will appear during fasting when the body relies on liver glucose
What is Type 2 (Pompe’s disease)?
A deficiency in alpha-1,4-glucosidase activity in lysosomes. Causes death by cardiorespiratory failure
What is Type 3 (Cori’s disease)?
Deficiency in amylo-1,6-glucosidase (debranching enzyme) resulting in hypoglycaemia. Symptoms often appear at puberty
What is Type 4 (Andersen’s disease)?
Liver glycogen is in normal amounts but is unbranched making it not very soluble. Sufferers don’t live beyond 5 years
What is type 5 (McArdle’s syndrome)?
Affects muscle glycogen phosphorylase so muscles cannot break down glycogen . Sufferers have a low tolerance for exercise and fatigue easily, with painful muscle cramps but have a normal life-span
