Download The Liver

The Liver
A2 Biology
Liver...
• The liver is a large active organ in the
abdominal cavity. It has numerous functions,
some important ones are:
regulation of blood sugar
production of and regulation of lipid
synthesis of plasma proteins
transamination to produce non-essential amino
acids
– deamination
– detoxification
–
–
–
–
• Before considering the production of urea and
detoxification in detail, you need to know a
little about the structure and histology of the
liver
• The liver is found in the upper right of
the abdominal cavity, just below the
diaphragm. It is made of several lobes
and has four connections:
– bile duct
– hepatic artery
– hepatic portal vein
– hepatic vein
Hepatic vein takes
blood back into the
general circulation. Its
composition is regulated
with excesses reduced
and shortages made up.
Bile duct takes bile
from the liver to the gall
bladder (for storage) or
to the small intestine
where it neutralises
excess stomach acid
and emulsifies lipids.
Hepatic artery brings
high pressure
oxygenated blood to the
liver. It is rich in O2 and
low in waste.
Hepatic portal vein
brings low pressure
blood from the intestine
to the liver. It is rich in
dissolved nutrients, low
O2 and high CO2.
• Liver has four connections:
– hepatic artery
• brings high pressure oxygenated blood from the
aorta.
– hepatic portal vein
• brings nutrient rich blood from the gut
• blood has already passed through the capillaries
of the small intestine
– at a much lower pressure than the blood of the hepatic artery
– partially deoxygenated
– hepatic vein
• returns blood to the general circulation
– bile duct
• takes bile from the liver to the gall bladder for
temporary storage
Histology of the liver...
• The liver is made up of 100 000 or so lobules
– cylindrical structures
– at their centre is a branch of the hepatic vein
– at the outside are branches of
• the hepatic artery
• hepatic portal vein
• Blood flows from the outer to the
central vessel
– through blood-filled channels or sinusoids
• lined with liver cells called hepatocytes
– hepatocytes regulate the composition of
the blood
• remove excess substances from the blood and
• secrete materials into it which are in short
supply or have been made by the liver
• Sinusoids are in rows that radiate out
from the centre
– hepatocytes are only ever one or two cells
thick
• diffusion path is short.
• Bile canaliculi are present
– blind-ending channels
– also lined by hepatocytes
• secrete bile into the channel
• flows away from the centre of the lobule to a
branch of the bile duct at the periphery.
• Sinusoids have large phagocytic Kupffer
cells
– capture and engulf any bacteria that
they encounter
• gut contains large numbers of bacteria and could enter
the circulation via the hepatic portal vein
– also destroy old red blood cells
– produce waste bilirubin from haemoglobin
• red-brown pigment excreted in bile
Peripheral vessels:
branches of hepatic
artery and hepatic portal
vein bring blood to the
lobule.
Central vessel: branch
of the hepatic vein
returns blood to the
general circulation.
Sinusoid lined with
hepatocytes: liver cells
remove excess
substances from the
blood and secrete
shortage substances into
the blood.
Liver: injected section of lobules with central and peripheral vessels.
Sinusoid lined with
hepatocytes: liver cells
remove excesses from and
secrete shortage substances
into the blood.
Central vessel: branch of
the hepatic vein which returns
blood to the general
circulation.
Liver: detail of central vessel and hepatocytes.
Macrophage or Kupffer
cell: engulfs pathogens and
removes damaged red cells
from the circulation. Produces
the bile pigment bilirubin.
Bile ductile: takes
bile to the gall bladder
for temporary storage.
Bile emulsifies fats.
Branch of hepatic
portal vein: brings
blood rich in nutrients
to the liver from the
gut.
Kupffer cell or
macrophage: engulfs
bacteria and old or
damaged red blood cells.
Bile canaliculus: a blind
ending canal into which
bile is secreted by the
hepatocytes.
Blood sinusoid: a
blood-filled space lined
with hepatocytes.
Central vessel: takes
blood to the hepatic
vein to be returned to
the general circulation.
Branch of hepatic
artery: brings high
pressure oxygenated
blood to the liver.
Hepatocyte or liver
cell: controls composition
of blood, detoxifies and
produces bile.
Formation of urea by liver...
• Excess amino acids cannot be stored in the
body
– have about the same energy as carbohydrates
– extremely wasteful if they were excreted
• Instead, they are deaminated by the liver
– amino group is removed to produce ammonia
– leaves an organic acid
• respired or used to make carbohydrates and fats
• Ammonia is very soluble and highly toxic
– converted to urea via the ornithine cycle
• sometimes called the ornithine-citrulline cycle
• energy-dependent reactions add it to CO2 to make urea
NH2
COOH
Amino acid – excess
cannot be stored, so it
is deaminated in the
liver
2NH3 +
Ammonia
CO2
Carbon
dioxide
COOH
Organic acid – can
be respired or
converted to lipid
and carbohydrate
CO(NH2)2
Urea
+
+
NH3
Ammonia –
converted to urea
for excretion
H2O
Water
NH3
CO2
Ornithine cycle:
H2O
The ornithine cycle is an
energy-consuming process that
converts toxic NH3 into urea.
In the cycle, TWO molecules of
Citrulline
Ornithine
NH3
NH3 are added to CARBON
DIOXIDE to produce urea.
Urea is still soluble, but is less
Arginine
H2O
toxic than ammonia. It is
secreted into the blood by the
HEPATOCYTES (liver cells) and
CO(NH2)2
H2O
transported to the KIDNEY for
excretion.
• The resulting urea is excreted
– in solution
– in urine
– via the kidney
• Not all animals use urea as their main
nitrogenous excretory product
– fish and aquatic animals
• often use ammonia
• can be diluted so not toxic
– birds, terrestrial reptiles and insects
• often excrete a uric acid paste
• to conserve water
Role of the liver in
detoxification...
• The liver detoxifies many substances
– For example, alcohol, drugs, antibiotics and
hormones
– converts them to harmless substances or
– excretes them into the bile.
• Much of the detoxification takes place
on the smooth endoplasmic reticulum in
the hepatocytes.
Alcohol detoxification...
• Alcohol is toxic and is broken down by the liver.
– involves the conversion of ethanol into ethanal and
– then to ethanoate
– ethanoate then enters Krebs cycle to produce
energy and ATP
• Ethanol contains a lot of energy
– can be a significant energy intake for some
individuals
– pure alcohol contains 29kJ g-1
• Detoxification is summarised on the next slide:
ethanol
ethanol
dehydrogenase
ethanal
dehydrogenase
ethanal
(acetaldehyde)
oxidised
NAD
reduced
NAD
oxidised
NAD
ethanoate
(acetate)
reduced
NAD
Alcohol abuse...
• If large quantities of alcohol are
consumed on a regular basis, the liver
can be damaged
• It can cause
– fatty liver
– hepatitis and
– cirrhosis
• Explain or comment upon the following
observations:
Q: The conversion of ethanol to ethanoate needs a supplyoxidised NAD. Other processes also need a supply of
NAD, e.g. oxidation of fatty acids. Why does excessive
alcohol consumption lead to a condition known as fatty
liver?
• The supply of available NAD is used for detoxification
of the alcohol so it is not available for other aspects of
metabolism, including the oxidation of fatty acids. Fatty
acids then accumulate.
• Also, ethanoate
– is fed into Krebs cycle where it is oxidised – less
need for oxidation of fatty acids to provide energy
– can be used to produce fatty acids
The fat that accumulates in ‘fatty liver’
is stored in the hepatocytes. What
effect might this have on hepatocyte
function?
• Fat is stored in droplets
– cells swollen
– disrupts normal cell functions
– particularly intracellular transport
• Condition is reversible
What is cirrhosis of the liver and what are
its effects on liver function?
(you might want to consider lobule structure, blood supply, effect on specific aspects
of metabolism, e.g. conversion of ammonia to urea and detoxification of hormones)
• Hepatocytes damaged and replaced by fibrous,
collagen-rich tissue.
• Liver cells regenerate
– but normal lobule structure lost
– poor blood supply to hepatocytes so
• Liver function declines
– ammonia not converted to urea, so increased toxicity
– hormones not detoxified, so effective concentration
increases