Transcript 15.3 Homeostasis - Liver Functions

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The Mammalian Liver
The liver is the largest gland in the body and
the second largest organ after the skin
The liver is situated under the diaphragm on
the right side of the abdominal cavity
Numerous metabolic reactions occur within the
liver and it is an important organ of homeostasis
Blood
Supply
The liver receives blood from two sources
The hepatic artery delivers
oxygenated blood to the liver
Blood leaves the liver
along the hepatic vein and
enters the vena cava
The hepatic portal vein delivers
blood, rich in digested food molecules,
from the small intestine
The Mammalian Liver
The liver is composed of a large
number of lobules
Each lobule contains many vertical rows of
liver cells (hepatocytes) arranged radially
around a central blood vessel called
the central vein
Branches of the hepatic artery and hepatic
portal vein supply blood to the capillaries
(sinusoids) of each lobule
Running between the lobules in the opposite
direction to the blood, are fine ducts
(canaliculi), carrying bile from the liver cells
towards the main bile duct
The Liver Lobule
Central vein of lobule
(to hepatic vein)
Blood flows from branches of
the hepatic portal vein and
hepatic artery along sinusoids
(dilated capillaries) between
the liver cells
Plates of liver
cells (hepatocytes)
An enlarged portion
of the liver lobule
provides further detail
Branch of hepatic
portal vein
Sinusoid
Canaliculus
Bile
duct
Network of canaliculi between
liver cells
Branch of
hepatic artery
Fine channels, called canaliculi, collect bile from
the liver cells and carry it towards the bile duct
Central vein of lobule
Branch of hepatic
(to hepatic vein)
portal vein
Phagocytic
Liver cells;
Hepatocytes
Sinusoid Kupffer cell
Part of Liver Lobule
blood
flow
Branch of
hepatic
artery
molecules enter
liver cells
flow of
bile
blood flows
into central vein
bile from
liver cells
Branch to
Bile canaliculus
bile duct
Hepatocytes bear numerous microvilli at their surfaces in contact with the
sinusoids, thereby increasing the surface area for facilitating the exchange of
materials; numerous mitochondria within the cytoplasm reflects their high
demand for ATP to provide for the numerous endergonic reactions
Sinusoids
Sinusoids are dilated capillaries in which the lining
epithelial cells and basement membrane are discontinuous
Sinusoids have larger diameters than other capillaries with
distinct gaps in their lining
Epithelial lining
cells
Basement
membrane
The structure of the sinusoidal capillaries allows for the ready
exchange of materials (including macromolecules) between
the blood and the liver cells
Sinusoids
Rows of liver cells
(hepatocytes)
Central Vein
Protein Metabolism
Lipid
Metabolism
Carbohydrate
Metabolism
Storage of
Vitamins and
Minerals
Haemoglobin and
Hormone breakdown
and Detoxification
Bile
Production
Carbohydrate Metabolism
The liver’s major role in the metabolism of
carbohydrates is that of glucose homeostasis
Under the influence of the hormones insulin and
glucagon (secreted by the Islets of Langerhans of
the pancreas) and adrenaline from the adrenal
glands, blood glucose concentrations are
regulated and adjusted to meet the metabolic
demands of the tissues
The digestion of polysaccharides and
disaccharides in the gut yields the
monosaccharides glucose, fructose and
galactose; these sugars are transported to
the liver along the hepatic portal vein
Carbohydrate Metabolism
In the liver, most of the fructose and
galactose molecules are converted to glucose;
the liver plays a significant role in the control
of blood glucose concentrations
in three major ways:
• Glycogenesis; activation of the liver enzymes that
convert glucose into glycogen for storage
• Glycogenolysis; activation of the liver enzymes
that convert glycogen into glucose when blood
glucose levels fall
• Gluconeogenesis; activation of the liver enzymes
that convert non-carbohydrates into glucose in
response to low blood glucose concentrations
Glycogenolysis; the conversion
of stored glycogen into glucose
when blood sugar levels fall
glucagon and adrenaline
Glycogenesis; the conversion
of glucose into glycogen when
blood sugar levels rise
insulin
Gluconeogenesis is the conversion of
non-carbohydrates, such as amino acids
and glycerol, into glucose by the liver
When the demand for
glucose depletes the glycogen
stores, non-carbohydrate
sources are converted by the
liver into glucose
Protein Metabolism
During digestion, proteins are hydrolysed into
their constituent amino acids and transported to
the liver along the hepatic portal vein
Unlike glucose, excess amino acids cannot be
stored in the liver; excess dietary amino acids
undergo deamination and are also converted
into glucose and triglycerides
Transamination reactions occur in the liver;
this involves the conversion of one amino acid
into another and is the process by which
non-essential amino acids are synthesised
Protein Metabolism
The fate of surplus amino acids within
the liver cells involves:
• Deamination; the removal of the amino group from
an amino acid, producing ammonia and a keto
acid; the toxic ammonia is converted into urea,
which is transported to the kidneys for excretion;
the keto acid may enter the respiratory pathway to
yield ATP or, may be used for the synthesis of
glucose and fatty acids
• Gluconeogenesis; liver cells can convert amino
acids into carbohydrate
• Lipogenesis; liver cells can convert amino acids
into fats
Surplus amino acids cannot be stored
and undergo deamination in the liver
The highly toxic ammonia
enters the ornithine cycle
and is converted into urea
The amino group
of the amino
acid, together
with a hydrogen
atom, is removed
to form ammonia
and a keto acid
The keto acid either
enters the respiratory
pathway and generates
ATP, or it is converted
into carbohydrates or
fats
The less toxic
urea is excreted
by the kidneys
deamination
conversion to
urea in the
ornithine cycle
Excretion by
the kidneys
respired
converted to
carbohydrates
or fats
ATP
Transamination involves the transfer of
an amino group from a donor amino acid
to a recipient keto acid; the donor amino
acid becomes a keto acid and the recipient
keto acid becomes an amino acid
All non-essential
amino acids may
be synthesised by
transamination
Lipid Metabolism
The lipids are a diverse group of
molecules and include cholesterol,
triglycerides and phospholipids
The liver synthesises, modifies, releases and
eliminates lipids, playing a major role in
their homeostatic regulation
Surplus cholesterol and phospholipids are
eliminated in the bile; the liver manufactures
bile, which is stored in the gall bladder and
secreted into the duodenum of the gut
Lipid Metabolism
The roles of the liver in lipid metabolism include:
• Lipogenesis; the synthesis of triglycerides from
glucose when glycogen stores are depleted; the
resulting triglycerides can be stored or utilised in
the production of cholesterol and phospholipids
• The synthesis of cholesterol and phospholipids
• The modification of cholesterol and triglycerides
(combined with liver proteins) to produce
water-soluble lipoproteins for transport to
other body tissues
• The elimination of surplus cholesterol and
phospholipids in the bile
Liver cells synthesise
triglycerides from glucose
or amino acids (lipogenesis)
when glycogen stores are full
The liver synthesises most of
the cholesterol and
phospholipid found in the
body and regulates their
concentrations in the blood
Excess cholesterol and
phospholipid is removed in
the bile and delivered to the
gut for elimination
The resulting triglycerides can
be stored or used to synthesise
other lipids, such as cholesterol
and phospholipids
The synthesis, release and
elimination of cholesterol
and phospholipids is
regulated by the liver
Cholesterol and
triglycerides are combined
with liver proteins to render
them soluble for transport
in the blood (lipoproteins)
Surplus cholesterol and
phospholipid is eliminated in the bile
‘Good’ and ‘Bad’ Cholesterol
Low density lipoproteins (LDLs) are loosely termed
‘bad cholesterol’ since excess LDLs remain in the
bloodstream and deposit cholesterol in and around the
muscle fibres in arteries (forming fatty plaques); this
may lead to atherosclerosis (narrowing of the arteries)
LDLs attach to specific receptors on the surfaces
of cells and are taken into the cells by
endocytosis where the cholesterol is released
When a cell’s cholesterol needs are met, the production
of LDL receptors is shut down, and the receptors
already present are gradually removed; the lack of
receptors raises plasma LDL levels, making it more
likely that plaques will develop in the arteries
Fatty deposits
begin to build up
in the artery wall
Fatty deposits (plaques) build
up in large quantities; calcium
deposits harden the arteries;
blockage is extreme and blood
flow is seriously affected
‘Good’ and ‘Bad’ Cholesterol
High density lipoproteins (HDLs) are associated
with a decreased risk of atherosclerosis
HDLs remove excess cholesterol from body cells
and transport it to the liver for elimination;
accumulation of cholesterol in the blood is
prevented and the risk of fatty plaque formation
in the arteries is reduced