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The
Liver
1450 cm3 of blood
flows through the
liver every minute
minute.
Wide range of
functions;
1)Amino acids to
glucose.
7) Detoxification
6) Production of
bile.
2)Metabolism
of fat.
3) Synthesis of
Triglycerides.
5) Deamination/
transamination/
urea formation
4) Synthesis & regulation
of cholesterol.
A – Liver
B – Hepatic vein
C – Hepatic artery
D – Portal vein
E – Bile duct
F – Stomach
G – Cystic duct
H – Gall bladder
Blood enters the
liver through two
vessels:
1) Hepatic artery
2) Portal vein
3x the blood enters via the Portal vein.
The blood here comes from the small intestine
it is rich is dissolved nutrients.
The blood here is deoxygenated and at low pressure
compared to the hepatic artery
VENA CAVA
Stomach
Liver
Pancreas
Small intestine
AORTA
Histology of the liver……
Liver Lobule.
Central vein
HP vein
Hepatic artery
Bile duct
2mm
Histology of the liver……
There are 10,000
lobules one adult liver
Blood flows up thru.
HPV & hepatic art.
Blood then flows thru.
into Central vein thru.
SINUSOIDS
Blood then flows to
hepatic vein & out
HPV
HA
Lobules are made of
Cells called HEPATOCYTES
Histology of the liver……
Bile ducts
Special cells produce
bile, which flows thru.
BILE CANALICULI.
Special cells (KUPFFER)
are macrophages that eat
bacteria that come in blood
From the HPV
2mm
CBH metabolism in the liver……
Liver stores glycogen and
Hepatocytes respond to insulin
& glucagon
GLYCOGEN
25% LIVER
75% MUSCLES
GLUCOSE
INSULIN
GLUCAGON & ADRENALINE
GLYCOGEN
Glycogen formed
INSULIN
High blood
Glucose level
This occurs in
HEPATOCYTES
Blood glucose
drops
βcells in the Islets of
Langerhans secrete INSULIN
Glycogen
GLUCAGON & ADRENALINE
Low blood
glucose level
This occurs in
HEPATOCYTES
High blood
glucose level
αcells in the Islets of
Langerhans secrete GLUCAGON
CBH metabolism in the liver……
……GLUCONEOGENESIS
Gluconeogenesis – literally ‘making new glucose’
3 biological molecules can be broken down to form glucose;
AMINO ACIDS, LACTATE & LIPIDS.
3 biological molecules are initially broken down to form
triose sugars (3C), which are then metabolised into glucose.
There are 3 biochemical pathways, each of which are only
used when glucose concentrations are low.
CBH metabolism in the liver……
……GLUCONEOGENESIS
Amino Grp (-NH2)
removed
Excess
amino
acids
Urea formed
DEAMINATION
Glucose
Pyruvate
Triose phosphate
CBH metabolism in the liver……
……GLUCONEOGENESIS
Fatty Acids
Excess
lipids
HYDROLYSIS
Glucose
Glycerol
Triose phosphate
CBH metabolism in the liver……
……GLUCONEOGENESIS
Lactate
Pyruvate
Triose
phosphate
What is Lactate?
By product of anaerobic respiration,
very common in large muscles.
Glucose
Lipid metabolism in the liver……
Gluconeogenesis only occurs when blood glucose levels
are low. When glucose levels are high, lipids are
produced.
So excess glucose forms lipids, lipids are needed for;
Formation of steriods,
which then form hormones
Cell structures (membranes)
Energy store in adipose cells
Used in respiration to produce ATP
Lipids as an energy source……
Lipids are used as energy sources even when blood
glucose levels are high.
Often fatty acids are used as a preferred energy
source, this is particularly true of cardiac muscle.
Triglycerides are broken down into glycerol and fatty
acids (hepatocytes),the fatty acids are broken down
into acetyl coenzyme A, this is then fed into the Krebs
Cycle, producing ATP.
Triose
phosphate
1
Glycerol 3 fatty acids
Glucose
Glycerol
TRIGLYCERIDE
2
Acetyl
Coenzyme
A
Lipids as an energy source……
KREBS
CYCLE
ATP
Synthesising triglycerides……
Once lipids are synthesised, they are converted to
TRIGLYCERIDES and then stored in adipose tissue.
But, lipids are insoluble in water, meaning they are
difficult to transport.
They are converted to LIPOPROTEINS as low density
lipoproteins (LDLs)
For each fat that needs transporting, there is specific
lipoprotein that does the job – the all have different
densities.
Synthesising & regulating cholesterol……
The liver makes cholesterol.
Cholesterols functions are:
1) Cell membrane stability.
7) Involved in synthesis of
2) Cell membrane fluidity. bile salts.
3) Membrane barrier to
hydrophilic substances.
4) Synthesis of steroid
hormones (oest/test)
6) Involved in Vit D synthesis.
5) Deposited under skin,
making it waterproof.
Synthesising & regulating cholesterol……
Meat, eggs and other
diary products have
high cholesterol.
When you eat lots of
these foods, your liver
synthesises less
cholesterol.
This is called dietary
cholesterol.
So high levels of DIETARY
CHOLESTEROL
does not always lead to high
BLOOD CHOLESTEROL
CHOLESTEROL
..Enzymes
High levels of dietary
cholesterol stops……
Acetyl
Coenzyme A
Synthesising & regulating cholesterol……
Alternatively, if your
diet contains high levels
of SATURATED FATS…
…synthesis of
cholesterol increases.
Lots of evidence to
suggest that genetics
Has a role to play
No C-C double bonds,
e.g. all C-H bonds
Transporting cholesterol……
Cholesterol is a lipid,
therefore not water
soluble.
High Density Lipoproteins HDLs
These are good for you.
Protecting you from LDLs
May also remove LDLs
It is also transported
in LIPOPROTEINS.
It is transported as
either…….
Low Density Lipoproteins LDLs
These are not good for you.
They deposit cholesterol on
walls of arteries (AKA plaques)
Protein metabolism……
Production of 3 blood proteins –
FIBRINIGEN/ALBUMIN/GOBULINS
Production of urea –
linked to
DEAMINATION.
Convert one amino acid
to another - AKA
TRANSAMINATION.
Removing excess amino
acids - AKA
DEAMINATION.
TRANSAMINATION -
converting one amino acid to another.
If our dietary intake of amino acids does not match the
bodies requirements, then the liver has the ability to
add/remove elements from R groups inorder to make new
amino acids.
There are a group of amino acids that the body can not
do this with, they are called ESSENTIAL AMINO
ACIDS.
DEAMINATION –
removing excess amino acids.
If our dietary intake of amino acids exceeds the bodies
requirements, then the excess needs to be removed.
Deamination removes the AMINE GRP (-NH2), with the
rest of the molecule being converted to CBH or fat.
The AMINE GRP (NH2) is converted to AMMONIA (NH3) –
this is very soluble and toxic, so is not around for long!
It is then combined with CO2 using ATP to produce UREA
(CO(NH2)2 this occurs in the ornithine cycle.
The ORNITHINE CYCLE.
Deamination
CO2
NH3
ATP
ATP
UREA
CO(NH2)2
SYNTHESIS of PLASMA PROTEINS………
There are 3 important proteins in blood;
•Fibrinogen
•Globulin
•Albumin
Each of these proteins are globular and are produced in
the liver.
Hwrk: Read and make notes
on
GLOBULIN & ALBUMIN (pg 24).
SYNTHESIS of PLASMA PROTEINS………
Damage to blood vessels
leads to the collagen fibres
being exposed, this stimulates
platelets.
Prothrombin
Fibrinogen
Thrombin
Fibrin
Thrombin – an enzyme, which catalyses the removal of AA
from fribrinogen, to allow it to polymerase and form FIBRIN.
Fibrin is an insoluble protein that forms long fibres, they
tangle up trapping rbcs and leading to a clot.
Production of BILE………
Bile ducts
Special cells produce
bile, which flows thru.
BILE CANALICULI.
1000cm3 of bile is
produced each day
Cholesterol made in the
Liver is needed to prd. bile
2mm
Bile to gall
bladder
Production of BILE………
BILE is composed of water & BILE SALTS.
BILE SALTS emulsify fats, then LIPASE can act on the
larger surface area.
BILE SALTS also contain cholesterol – if there is too much
cholesterol or not enough water, gall stones can form.
They can block bile duct and interfere with lipase
digestion.
BILE & dead RBCs………
RBCs only live for about 120 days, then they are broken
down in the spleen.
(below the heart, lower than the diaphragm).
HAEMOGLOBIN is broken down in the LIVER into HAEM &
GLOBIN.
GLOBIN is broken down into its constituent AA, these are
then recycled.
HAEM is broken down into iron and the greenish yellow
product called BILIRUBIN – this is excreted into bile.
DETOXIFICATION
Many drugs/dangerous substances are broken down in the
smooth endoplasmic reticulum of hepatocytes.
Metabolising alcohol
•Alcoholic drinks contain ethanol (C2H5OH)
•It is lipid soluble, so moves thru. cells very easily.
•Alcohol dehydrogenase catalyses the breakdown of ethanol
to ethanal.
•Aldehyde dehydrogenase then catalyses the breakdown of
ethanal to ethanoate
•Ethanoate can then enter the Krebs cycle to produce ATP.
DETOXIFICATION of ALCOHOL
ALCOHOL
DEHYDROGENASE
ETHANOL
Oxidised
NAD
ALDEHYDE
DEHYDROGENASE
ETHANAL
Reduced
NAD
ETHANOATE
Oxidised Reduced
NAD
NAD
The KREBS
CYCLE
If you drink too much, reduced NAD builds up and levels of
oxidised NAD become low. These means fatty acids build and
a condition called ‘fatty liver’ develops.
DETOXIFICATION of ALCOHOL
Drinking too much leads to......
•Low levels of oxidised NAD, failure to metabolise fatty
acids and ‘fatty liver’ develops.
•Destruction of hepatocytes, leads to replacement with
inferior hepatocytes.
•Reduced blood supply to the lobules
•This is called CIRRHOSIS
The liver can not function properly, e.g. NH3 builds up and can
Lead to coma and death in extreme cases