The Liver. 1450 cm 3 of blood flows through the liver every minute. Wide range of functions; 1)Amino acids to glucose. 1450 cm 3 of blood flows through.

The Liver

1450 cm3 of bloodflows through theliver every minute.

Wide range offunctions;

1)Amino acids to glucose.

1450 cm3 of bloodflows through theliver every minute

2)Metabolism of fat.

3) Synthesis of Triglycerides.

4) Synthesis & regulationof cholesterol.

5) Deamination/transamination/urea formation

6) Production ofbile.

7) Detoxification

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 twovessels:

1)Hepatic artery2)Portal vein

3x the blood enters via the Portal vein.

The blood here comes from the small intestineit is rich is dissolved nutrients.

The blood here is deoxygenated and at low pressure compared to the hepatic artery

Small intestine

Liver

Stomach

Pancreas

AORTA

VENA CAVA

Histology of the liver……

2mm

Liver Lobule.

Central vein

HP vein

Hepatic arteryBile duct

Histology of the liver……

There are 10,000 lobules one adult liver

Blood flows up thru.HPV & hepatic art.

HPV

HA

Blood then flows thru.into Central vein thru.SINUSOIDS

Lobules are made of Cells called HEPATOCYTES

Blood then flows tohepatic vein & out

2mm

Histology of the liver……

Bile ducts

Special cells producebile, which flows thru.BILE CANALICULI.

Special cells (KUPFFER)are macrophages that eat bacteria that come in bloodFrom the HPV

CBH metabolism in the liver……Liver stores glycogen and

Hepatocytes respond to insulin& glucagon

GLUCOSE

GLYCOGENGLUCAGON & ADRENALINE

INSULIN

GLYCOGEN25% LIVER

75% MUSCLES

High bloodGlucose level

βcells in the Islets ofLangerhans secrete INSULIN

INSULIN

Glycogen formed

Blood glucosedrops

This occurs inHEPATOCYTES

Low bloodglucose level

αcells in the Islets ofLangerhans secrete GLUCAGON

GLUCAGON & ADRENALINE

Glycogen

This occurs inHEPATOCYTES

High bloodglucose level

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 formtriose 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

Excess aminoacids Glucose

DEAMINATION

Amino Grp (-NH2) removed

Urea formed

Pyruvate Triose phosphate

CBH metabolism in the liver……

……GLUCONEOGENESIS

Excess lipids

Glucose

HYDROLYSIS

Fatty Acids

Triose phosphate

Glycerol

CBH metabolism in the liver……

……GLUCONEOGENESIS

Lactate GlucoseTriose

phosphate

Pyruvate

What is Lactate?By product of anaerobic respiration, very common in large muscles.

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;

Energy store in adipose cells

Used in respiration to produce ATP

Cell structures (membranes)

Formation of steriods, which then form hormones

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.

Glycerol3 fatty acids

TRIGLYCERIDE

GlycerolGlucose

Triose phosphate1

2

AcetylCoenzyme

A

ATP

KREBSCYCLE

Lipids as an energy source……

Synthesising triglycerides……Once lipids are synthesised, they are converted toTRIGLYCERIDES 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 specificlipoprotein that does the job – the all have different densities.

Synthesising & regulating cholesterol……

The liver makes cholesterol.Cholesterols functions are:1) Cell membrane stability.2) Cell membrane fluidity.3) Membrane barrier tohydrophilic substances.

4) Synthesis of steroid hormones (oest/test)

5) Deposited under skin, making it waterproof.

6) Involved in Vit D synthesis.

7) Involved in synthesis of bile salts.

Synthesising & regulating cholesterol……

Meat, eggs and other

diary products have high cholesterol.

When you eat lots of these foods, your liver synthesises lessless cholesterol.

This is called dietary cholesterol.

High levels of dietary cholesterol

stops……

Acetyl Coenzyme

A

CHOLESTEROL

..Enzymes

So high levels of DIETARY CHOLESTEROL

does not always lead to high BLOOD CHOLESTEROL

Synthesising & regulating cholesterol……

Alternatively, if your diet contains high

levels of SATURATED FATS…

…synthesis of cholesterol increases.

No C-C double bonds,

e.g. all C-H bonds

Lots of evidence to suggest that

geneticsHas a role to play

Transporting cholesterol……

Cholesterol is a lipid, therefore not

water soluble.

It is also transported in LIPOPROTEINS.

It is transported as either…….

High Density Lipoproteins HDLs

These are good for you.Protecting you from LDLs

May also remove LDLs

Low Density Lipoproteins LDLs

These are not good for you.They deposit cholesterol on

walls of arteries (AKA plaques)

Protein metabolism……

Convert one amino acid to another -

AKATRANSAMINATION.

Removing excess amino acids - AKA

DEAMINATION.

Production of urea – linked to

DEAMINATION.

Production of 3 blood proteins – FIBRINIGEN/ALBUMIN/GOBULIN

S

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 NH3

CO2

ATP

ATP

UREACO(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 vesselsleads to the collagen fibres

being exposed, this stimulatesplatelets.

Prothrombin

Thrombin

Fibrinogen

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………

2mm

Bile ducts

Special cells producebile, which flows thru.BILE CANALICULI.

1000cm3 of bile is produced each day

Cholesterol made in theLiver is needed to prd. bile

Bile to gallbladder

Production of BILE………

BILE is composed of water & BILE SALTS.

BILE SALTS emulsify fats, then LIPASE can act on thelarger surface area.

BILE SALTS also contain cholesterol – if there is too muchcholesterol 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.

DETOXIFICATIONMany drugs/dangerous substances are broken down in thesmooth 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.

ETHANOL ETHANAL ETHANOATE

The KREBS CYCLE

ALCOHOLDEHYDROGENASE

ALDEHYDEDEHYDROGENASE

Oxidised NAD

Reduced NAD

Reduced NAD

Oxidised NAD

DETOXIFICATION of ALCOHOL

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 canLead to coma and death in extreme cases