it's a quite an important one one of the
more important of course but it's think
about another function of the liver and
then what I want to think about now is
ketogenesis the liver will produce
ketones and this happens particularly
under the influence of the hormone
glucagon release from the alpha cells in
the pancreatic islets and lon
now in individual liver cells in the
hepatocyte there's lots of individual
liver cells and the individual liver
cells are very large amounts of
mitochondria
hundreds are maybe a thousand or more
per cell with these mitochondria with
their highly in folded inner membranes
and these are the powerhouses of the
cell where internal respiration and
energy production goes on so the liver
cells contain many many mitochondria
they contain lots of mitochondria now a
blood sugar levels drop blood sugar
levels drop that's detected by the alpha
cells of the pancreatic islets and in
response to this hypoglycemic stimulus
they will produce glucagon and glucagon
will do various things so to begin with
for example glucagon will facilitate
gluco neo lysis breaking glycogen down
into glucose but we only store enough
glycogen for a few days of starvation
after that when the glucagon has caused
the glycogen to be released into glucose
and we've used that up with run out of
run out of a glycogen then then we need
other processes and in that case the
glucagon will stimulate ketogenesis when
blood sugar levels alone for example as
occurs in starvation so when there's
metabolic activity in the mitochondria
in the absence of glucose then ketones
will be produced so ketones are produced
when there is low levels of
goes inside the individual hepatocyte
and what the individual hepatocyte will
do is they will take in fatty acids and
some some ketogenic amino acids but
largely fatty acids and the fatty acids
will be converted in the liver and the
apat asides will produce huge amounts of
these ketones
so the vast majority of ketones that
occur in the blood in starvation have
been produced by the liver cells and
these ketones have been traditionally
referred to as ketone bodies this is
just historical term ketone bodies but
there's actually three of them there are
actually three chemicals
so there's b2 hydroxy butyrate that's
that one there's a Seto acetate and
there's acetone and of course the
acetone is the one which is very
volatile and you can smell that on the
breath of Sawin whose ketotic so that
ketotic smell you get is lized from the
acetone and the beta hydroxy butyrate
and the acetyl acetone these are both
acidic so when there's a lot of ketones
that's often associated with a reduction
in pH in the blood with with a relative
acidosis and if the ketoacidosis is
severe then the normal blood buffering
systems can be overcome and the pH can
actually drop resulting in an actual
acidosis meaning that patient E is very
sick of course and we largely associate
this with with diabetes so ketosis and
the release of ketone bodies will occur
in starvation for the simple reason that
these are able to be used by the cells
of the body to produce energy instead of
glucose so the brain over time the heart
the skeletal muscles can all use the
ketone bodies as their energy substrate
as an alternative to glucose now of
course we stress that the brain must
have a constant supply of glucose and
that's true but over time the brain can
adapt
to use more ketone bodies and relatively
less glucose to supplies energy but it
does take time to facilitate that
adaptation but it but it does happen
so the ketone bodies are the body's
emergency fuel supply and of course
these can carry on being produced as
long as we've got a few proteins left
and some fatty acids and of course how
long they're going to last for depends
how many fats are stored in the body but
fats from all over the body can be
mobilized go to the liver cells undergo
this process of ketogenesis while being
stimulated by glucagon which stimulates
this process resulting in the production
of these ketone bodies which we can use
as energy but of course the irony and
diabetus is that there's lots of glucose
in the blood but that glucose in
diabetes can't get into the individual
cells so in diabetes the the glucose is
in the blood
plenty of glucose in the blood but you
need the insulin to transport the
glucose into the cells without the
insulin the glucose stays outside the
cells while the mitochondria are within
without glucose so though within the
cell but that there without glucose and
that's what causes ketogenesis if there
is insulin lack so the irony is the
patient can be actually hypoglycemic but
still ketogenic whereas in starvation
what I guess you could say this
mechanism is designed for is the patient
will be hypoglycemic very low on sugar
so the body is in making me the key
terms as an alternative emergency fuel
supply quite amazing the way the body is
designed to survive and deliver can
facilitate that process via ketogenesis
you