hypoglycaemia

Question 1

what is hypoglycaemia

Answer 1

blood glucose level of below 4mM (72mg/dL)

Question 2

what are the symptoms of hypoglycaemia

Answer 2

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

Question 3

further symptoms of hypoglycaemia

Answer 3

equiv to cerebral anoxia inc moodiness, faintness, numbness in arms and hands, blurred vision, confusion, memory loss, dizziness, lethargy which can progress to coma

Question 4

consequences of hypoglycaemia

Answer 4

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

Question 5

causes of hypoglycaemia

Answer 5

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

Question 6

what causes alcohol induced hypoglycaemia

Answer 6

occurs on depletion of glycogen stores when blood glucose relies on hepatic gluconeogenesis (hours after alcohol ingestion)

Question 7

how does alcohol induced hypoglycaemia occur short term

Answer 7

places additional stress on gluconeogenesis as alcohol is metabolised primarily in liver by an unregulated process

Question 8

how does alcohol induced hypoglycaemia occur long term

Answer 8

gluconeogenesis dec by liver damage and reduced muscle mass

Question 9

how is alcohol metabolised

Answer 9

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+

Question 10

metabolic consequences of alcohol metabolism

Answer 10

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

Question 11

symptoms of alcohol induced hypoglycaemia

Answer 11

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)

Question 12

long term alcohol consumption effect on lipid metabolism

Answer 12

high NADH inhibits FA ox, FA synthesis occurs

TGs accumulate in liver - fatty liver (also exported as VLDL)

Question 13

how does fatty liver progress

Answer 13

liver inflamed causing damage to tissue (aka steatohepatitis)
scar tissue forms at sires of damage (fibrosis)
extensive scar tissue to replace healthy tissue (cirrhosis)

Question 14

long term alcohol consumption effects on efficiency of ethanol metabolism

Answer 14

acetate can be converted to acetyl-CoA but further processing prevented from high levels of NADH stopping citrate synthase and a-ketoglutarate dehydrogenase

Question 15

consequences of acetyl-CoA accumulation

Answer 15

production of KBs, released into blood and exacerbates acidic conditions from high lactate
processing acetate in liver inefficient so acetaldehyde builds up, highly toxic

Question 16

biochemistry of alcohol metabolism in liver

Answer 16

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

Question 17

what causes alcohol induced hepatomegaly

Answer 17

dec activity of proteasome
accumulation of protein, enlarging liver
also inc oxidative stress

Question 18

what deficiency is caused by alcohol consumption

Answer 18

deficient intake of micronutrients and minerals
50% thiamine deficient
symptoms inc anorexia, irritability, difficulties with short term memory

Question 19

what are the causes of thiamine (B1) deficiency

Answer 19

malnourishment
ethanol interferes with GI absorption
hepatic dysfunction, hinders storage and activation to thiamine pyrophosphate

Question 20

why is thiamine important

Answer 20

cofactor of many enzymes (glycolysis, TCA, PPP)

half life of 10-20 days so deficiency occurs rapidly on depletion

Question 21

What are glycogen storage diseases

Answer 21

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

Question 22

types of glycogen storage diseases

Answer 22

family inborn errors of metabolism, low freq
type 0 glycogen synthase
1 G6Pase
III debranching enzyme
IV branching enzyme
V glycogen phosphorylase

Question 23

what is type 1 disease

Answer 23

von gierke’s disease

affects mainly liver and kidneys caused by G6Pase deficiency

Question 24

what is type II disease

Answer 24

Pompe’s disease
deficiency of a1,4glucosidase activity in lysosomes
can be one of most devastating, caused death by cardiorespiratory failure

Question 25

what is type III disease

Answer 25

cori’s disease
deficient amylo1,6glucosidase
unable to break down glycogen = hypoglycaemia
symptoms disappear at puberty

Question 26

what is type IV disease

Answer 26

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

Question 27

what is type V disease

Answer 27

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

Question 28

how common is type 1 disease

Answer 28

most common GSD (25%)

Question 29

how does type 1 disease work

Answer 29

G6P-glucose + Pi
catalysis terminal reaction of glycogenolysis and gluconeogenesis
impaired exports of glucose from liver, between meals causes hypoglycaemia (no response to glucagon)

Question 30

symptoms off type 1 disease

Answer 30

appear when intervals between feeds increases and infants sleep through night or when illness stops normal feeding

Question 31

what does lack of G6Pase mean

Answer 31

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

Question 32

metabolism in type 1 disease

Answer 32

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

Question 33

signs of type 1 disease

Answer 33

enlarged liver and/or kidneys
stunted growth
sev tendencies to hypoglycaemia (convulsons), hyperlactaemia and hyperlipidaemia

Question 34

management and treatment of type 1 disease

Answer 34

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