hypoglycaemia Flashcards
what is hypoglycaemia
blood glucose level of below 4mM (72mg/dL)
what are the symptoms of hypoglycaemia
sweating, tachycardia and agitation due to activation of SNS and release of adrenaline and glucagon
may show at higher levels if rapid fall from prev elevated levels and some show not effects even below 4mg/dL
further symptoms of hypoglycaemia
equiv to cerebral anoxia inc moodiness, faintness, numbness in arms and hands, blurred vision, confusion, memory loss, dizziness, lethargy which can progress to coma
consequences of hypoglycaemia
serious effects on brain (loss of cognitive function, seizures and coma)
lose consciousness at 2.5mg/dL
rapid restoration essential and prolonged/repeated events can cause permanent brain damage
causes of hypoglycaemia
exercise
fasting
excess exogenous insulin
insulinoma - excess endogenous insulin
inhibiting endogenous glucose production (eg alcohol)
healthy - normally mild and due to exercise or fasting
other causes are hypernatraemia (eg diabetes insipidus)
hypovolaemia from vomitting/dehydration
pathologies such as adrenal insufficiency
what causes alcohol induced hypoglycaemia
occurs on depletion of glycogen stores when blood glucose relies on hepatic gluconeogenesis (hours after alcohol ingestion)
how does alcohol induced hypoglycaemia occur short term
places additional stress on gluconeogenesis as alcohol is metabolised primarily in liver by an unregulated process
how does alcohol induced hypoglycaemia occur long term
gluconeogenesis dec by liver damage and reduced muscle mass
how is alcohol metabolised
ethanol rapidly metabolised by alcohol dehydrogenase to acetaldehyde
req NAD+ as coenzyme
results in high NADH:NAD+ in cytosol
acetaldehyde transported to mt oxidised to acetate by acetaldehyde DH using NAD+
metabolic consequences of alcohol metabolism
lactate + NAD+ <> pyruvate NADH + H+
same for malate and oxaloacetate
G3P and DHAP
ethanol metabolism inc NADH + H+ snd shifts equilibrium of above reactions
reduces availability of substrates for entry to gluconeogenesis to maintain plasma glucose
symptoms of alcohol induced hypoglycaemia
stress response from fall of glucose (rapid HR, clammy) to enhance gluconeogensis by combined action of glucagon and adrenaline
rapid breathing physiologic response to metabolic acidosis (excess lactic acid)
long term alcohol consumption effect on lipid metabolism
high NADH inhibits FA ox, FA synthesis occurs
TGs accumulate in liver - fatty liver (also exported as VLDL)
how does fatty liver progress
liver inflamed causing damage to tissue (aka steatohepatitis)
scar tissue forms at sires of damage (fibrosis)
extensive scar tissue to replace healthy tissue (cirrhosis)
long term alcohol consumption effects on efficiency of ethanol metabolism
acetate can be converted to acetyl-CoA but further processing prevented from high levels of NADH stopping citrate synthase and a-ketoglutarate dehydrogenase
consequences of acetyl-CoA accumulation
production of KBs, released into blood and exacerbates acidic conditions from high lactate
processing acetate in liver inefficient so acetaldehyde builds up, highly toxic
biochemistry of alcohol metabolism in liver
ethanol from portal circulation to hepatocytes
converted to acetaldehyde (NAD+ - NADH)
enter mt to be convertered to acetate (inc NADH inc ROS)
some exported to other tissues, most converted to acetyl-CoA to KBs or fatty acyl-CoAs (DHAP to G3P to TG to VLDL to cont to hyperlipidaemia)
pyruvate to lactic acid - lactic acidaemia
hypoglycaemia in hepatic vein
what causes alcohol induced hepatomegaly
dec activity of proteasome
accumulation of protein, enlarging liver
also inc oxidative stress
what deficiency is caused by alcohol consumption
deficient intake of micronutrients and minerals
50% thiamine deficient
symptoms inc anorexia, irritability, difficulties with short term memory
what are the causes of thiamine (B1) deficiency
malnourishment
ethanol interferes with GI absorption
hepatic dysfunction, hinders storage and activation to thiamine pyrophosphate
why is thiamine important
cofactor of many enzymes (glycolysis, TCA, PPP)
half life of 10-20 days so deficiency occurs rapidly on depletion
What are glycogen storage diseases
inherited diseases where stores of glycogen affected by defects in enzymes of synthesis or degradation of glycogen
many different types (enzyme dependant)
all autosomal recessive except type IX (sex linked)
all result in production of abnormal amount/type of glycogen
types of glycogen storage diseases
family inborn errors of metabolism, low freq type 0 glycogen synthase 1 G6Pase III debranching enzyme IV branching enzyme V glycogen phosphorylase
what is type 1 disease
von gierke’s disease
affects mainly liver and kidneys caused by G6Pase deficiency
what is type II disease
Pompe’s disease
deficiency of a1,4glucosidase activity in lysosomes
can be one of most devastating, caused death by cardiorespiratory failure
what is type III disease
cori’s disease
deficient amylo1,6glucosidase
unable to break down glycogen = hypoglycaemia
symptoms disappear at puberty
what is type IV disease
Anderson’s disease one of most severe
liver glycogen in normal amounts but comprised on long unbranched chains with low solubility
sufferers rarely live beyond 5 years
what is type V disease
McArdle’s syndrome
affects muscle glycogen phosphorylase so muscle can’t breakdown glycogen (accumulates)
sufferers have low exercise tolerance and fatigue easily, painful cramps after exercise
normal lifespan
how common is type 1 disease
most common GSD (25%)
how does type 1 disease work
G6P-glucose + Pi
catalysis terminal reaction of glycogenolysis and gluconeogenesis
impaired exports of glucose from liver, between meals causes hypoglycaemia (no response to glucagon)
symptoms off type 1 disease
appear when intervals between feeds increases and infants sleep through night or when illness stops normal feeding
what does lack of G6Pase mean
glucose can’t be transported from liver
high G6P in liver and kidney, metabolised to lactic acid or converted to glycogen/lipid
results in
abnormal glycogen accumulation in liver and kidney (enlarge)
inc glycolysis - lactic acidosis
inc FA, TG, VLDL synthesis and excretion
metabolism in type 1 disease
body attempts to compensate for hypoglycaemia by releasing glucagon and adrenaline so fat stores mobilised and release FAs
converse to TGs and VLDL in liver - accumulation of fat in liver and hyperlipidaemia (can = hepatomas, looks for fat in both cheeks)
hyperuricaemia from hyperlactaemia as lactic acid in blood competes for kidney transport mechanisms
signs of type 1 disease
enlarged liver and/or kidneys
stunted growth
sev tendencies to hypoglycaemia (convulsons), hyperlactaemia and hyperlipidaemia
management and treatment of type 1 disease
correct hypoglycaemia and maintain normal blood glucose
young infants fed glucose via nasogastric tubes, older have glucose drinks 2-3 hour intervals day and night to stop fall in blood glucose and cerebral damage
uncooked cornstarch can prolong intervals between meals
restruct dietary lipids
liver transplant
