THE LIVER

SYLLABUS REQUIREMENTS5.4 The Liver

5.4.1 HistologyMetabolic role:CarbohydrateProteinLipid

Detailed structure of liver lobule.Glycogenesis, glycogenolysis and gluconeogenesis.Deamination, urea formation, transamination, plasma protein synthesis. Production of bile. Lipid metabolism.Summary diagram of the ornithine cycle and urea formation(molecular structures and site in the cell where each reaction takes place is not required).

Overview

A) THE POSITION AND STRUCTURE OF THE LIVER

B) LIVER FUNCTIONS

THE LIVER Position:beneath diaphragm – lies to the right of the stomach

The human liver:• normally weighs 1.5 kg • is both the largest:

internal organ gland in the human body

The liver:• is surrounded by a tough, fibrous capsule• shape of liver is variable

depending on amount of blood present

The liver has several lobes

The liver acts as a blood reservoir – holds about 10-15% of total blood

volume

• because of its rich blood supply, the liver regulates many activities associated with:

blood the circulatory system

Where is bile made?

What is the function of the gall

bladder?

Stores and concentrates bile

LIVER

Dual blood supply to liver

Oxygenated blood from heartBlood from

digestive system

HEPATIC PORTAL VEIN

HEPATIC ARTERY

LIVER

HEART

HEPATIC VEINto heart

GUT

Blood mixes inside the liver

Oxygenated blood

Blood rich in digested food

HEPATIC VEIN

Question: [MAY, 2004]

The hepatic portal vein is the only blood vessel in the human body within which the blood has a highly variable sugar content. Suggest an explanation for this. (2)

As the hepatic portal vein receives digested food from the gut, the amount of sugar present varies depending on the meal.

The liver is basically an organ of homeostasisIt controls many metabolic

activities essential for maintaining a constant blood compositionMany of the

liver functions are associated

with the metabolism of food brought from the gut

Lobules : the structural units of the liver each lobule has a diameter of

1mm hexagonal in shape over 100,000 present

lobule1mm

(a) Liver, as seen under a light microscope (TS)

Portal triad

Liver lobuleCentral vein [branch of hepatic vein]

A triad is present at each corner

(b) Single liver lobule

Portal triad

acinus

Acinus is the basic functional unit of

the liver

(c) Single Acinus

(d) Detail of Single Acinus

Bile canaliculus

Sinusoids

Sinusoids:are blood

spaces rather than blood

vessels

Blood flows slowly past the hepatocytes

Branch of hepatic artery

Branch of hepatic portal vein

Central vein

SinusoidBile canaliculusBile duct

Sinusoids:

radiate like the spokes of a wheel from the centre to the edges of the lobule

Blood & bile do not mix

Counter-current

flow

Jaundice

Cells found in the liver

Hepatocytes are the liver cells

Hepatocytes have:-prominent nuclei and Golgi

apparatus

many mitochondria (800-1000 per cell) & lysosomes

a lot of glycogen granules & fat droplets

Hepatocytes:are tightly packed together

have microvilli on their surface where they come in contact with blood vessels

The only other cells found in the liver are:- nerve cells cells associated with blood and

lymph vessels Kupffer (küppfer) cells macrophages Karl Kupffer [1829]

Kupffer cells are macrophages:Form part of the reticulo-endothelial system (part of the immune system involving phagocytes)

Kupffer cells & macrophages compared :both are phagocytes

Kupffer cells MacrophagesFixed to the walls of the sinusoids

Wander around in the liver

Function:1. break down old red

blood cells 2. ingest bacteria

identify and remove pathogens by phagocytosis

Liver Histology

Question: [MAY, 2004]

Distinguish between hepatocytes and liver lobules. (2)

Hepatocytes are the liver cells. Liver lobules are the structural units in the liver, consisting of masses of liver cells arranged around a central vein that is a terminal branch of one of the hepatic veins, and at whose periphery branches of the portal vein, hepatic artery, and bile duct are located.

Question: [SEP, 2001]Describe the role of the following cells that are found in the liver:–Küppfer cell (1)

Küppfer cells are macrophages resident in the liver which are phagocytic. Engulf pathogens and break down old red blood cells. –Macrophage (1)

Macrophages are wandering cells, not resident in liver, which engulf pathogens.

Overview

A) THE POSITION AND STRUCTURE OF THE LIVER

B) LIVER FUNCTIONS

The liver has: several hundred separate functions But only the following will be discussed

[as by syllabus]:1) Carbohydrate metabolism2) Protein metabolism3) Bile production4) Lipid metabolism

Functions of the liver :

1) Carbohydrate metabolism2) Protein metabolism3) Bile production4) Lipid metabolism

Role of Insulin

• sugars enter the liver from the gut by the hepatic portal vein

• the liver maintains the blood glucose level at approximately 90 mg glucose per 100cm3 of blood

• low levels of glucose would be particularly damaging because some tissues cannot store glucose e.g. the brain

The liver :1. Converts all hexose sugars to glucose

GluFru

Gal

The liver :2. Stores them as glycogen

(up to 100g in liver)

Glycogen(store)

Glucose phosphate

Glucose(free)

The conversion of glucose to glycogen is called: Glycogenesis

Which hormone stimulates glycogenesis?

Insulin

The breakdown of glycogen to glucose is called:

Glycogen(store)

Glucose phosphate

Glucose(free)

Phosphorylase (activated by glucagon) Three hormones can

stimulate glycogenolysis.

GlucagonAdrenalineCortisol

Glycogenolysis

Glycogen in the liver is broken down to glucose: To prevent the blood glucose level falling below 60 mg glucose per 100cm3 of blood

Glycogen also breaks down in:

1. times of danger 2. cold 3. stress

Gluconeogenesis is the synthesis of:glucose from non-carbohydrate sources- Lipids- Amino acids- Lactic acid

Gluconeogenesis happens when: the glycogen store in the liver is

exhausted.

LIVER

MUSCLE

SUMMARY [part 1]

SUMMARY [part 2]

What happens to lactate produced during anaerobic respiration in skeletal muscles?

Lactic acid (lactate) can be converted later into glucose and hence glycogen in the liver.

MUSCLE

LIVER

Low blood glucose levels (hypoglycaemia) stimulate :-

To satisfy immediate demand

1. the adrenal medulla to form adrenaline [Epinephrine]

2. hypothalamus to release ACTH-releasing hormone (adrenocorticotropin releasing hormone)

Cortisol

GLUCONEOGENESIS

HYPOTHALAMUS

ANTERIOR PITUITARY

ACTH

ADRENAL CORTEX

ACTH-releasing hormone

What happens to carbohydrate in the body which cannot be used or stored as glycogen?

Is converted into fats

and stored

Functions of the liver :

1) Carbohydrate metabolism2) Protein metabolism3) Bile production4) Lipid metabolism

2. PROTEIN METABOLISM

• Involves:-1. Deamination2. Urea formation [Ornithine

Cycle]3. Transamination4. Plasma protein synthesis

1. Deamination• is the process by which excess amino acids

are broken down• the amino group [NH2] is removed

Urea forms by a cyclic reaction:the Ornithine Cycle

Question: [MAY, 2005]

What is the ultimate fate of the urea produced during this process? (2)

excreted mostly in urine and to a lesser extent in sweat

Question: [SEP, 2013]This question is about the ornithine cycle and excretion.Briefly explain the importance of the ornithine cycle. (1)

It changes toxic ammonia into a less toxic substance which is urea.

2. Transamination

Is the synthesis of amino acids by the transfer of the amino group from an amino acid to

another organic acid [keto acid]

amino acid

amino acid

+ keto acid

NH2 NH2

+ keto acid

Transamination: an example

amino acid amino acidketo acid keto acid

Keto acid is an organic compound that contains a carboxylic acid group and a

ketone group.

Question: [SEP, 2001]Distinguish between the following pairs of processes that occur in the liver.

Deamination and Transamination (1)Deamination is the removal of the amino group from an amino acid which is in excess.

Transamination is the transfer of an amino group from an amino acid to an organic acid (keto acid).

Question: [SEP, 2001]

Glycogenesis and Gluconeogenesis (1)

Glycogenesis is when excess glucose is converted to glycogen.Gluconeogenesis is when glucose is formed from non-carbohydrate sources such as fats, lactic acid and amino acids.

4. Plasma Protein Production

Plasma Protein Production• Example:

a) Albuminb)Globulinc) Prothrombind)Fibrinogen

Albumin is the commonest proteinFunctions of albumin:1. to exert an osmotic pressure which opposes the

hydrostatic pressure developed in blood vessels.

In protein deficiency [Kwashiorkor] belly is swollen. Why?

Tissue fluid cannot be drained properly as osmotic pressure is not high.

Albumin is the commonest protein

Functions of albumin:

2. to act as transport molecules within the blood, carrying substances such as:

calcium bile salts some steroid hormones

Globulins: are very large molecules - and - globulins transport:-

–hormones (e.g. thyroxine and insulin)– cholesterol– lipids– iron– the vitamins B12 , A, D and K

Ruptured platelets &

damaged tissues

Thromboplastin

Calciumions Vitamin K

Prothrombin(inactive)

Thrombin(active)

Fibrinogen(soluble)

Fibrin(insoluble)

4. Prothrombin & Fibrinogen are involved in blood clotting

Functions of the liver :

1) Carbohydrate metabolism2) Protein metabolism3) Bile production4) Lipid metabolism

Bile contains:Bile pigments

are waste products from the destruction of old red blood cells

eliminated with the faeces

Bile salts emulsify fats

CholesterolSource:- synthesised in the liver-taken in with the diet

Needed to: - form bile salts

Functions of the liver :1) Carbohydrate metabolism2) Protein metabolism3) Bile production4) Lipid metabolism

Lipid Metabolism• the liver is involved in the:

- processing & transport of fats - rather than their storage

Liver cells :1. convert excess carbohydrate to fat

2. can remove cholesterol from the blood and break it down

3. can synthesise cholesterol from fat

4. if glucose is in short supply, the liver can break down fats into fatty acids and glycerol for respiration

Glycerol:can be converted to

glucose during gluconeogenesis

How are glycerol & fatty acids used in aerobic respiration?

Fatty acids:1. are converted to acetyl groups [2C fragment]

acetyl group + coenzyme A = acetyl coenzyme A [enters the Krebs cycle]

2. can be exported from the liver after conversion to other chemicals

Fats travel in the bloodstream as lipoproteins

a lipoprotein is composed of:

Core of fat and cholesterol

A protein cover, making it hydrophilic

Lipoproteins are classified according to their density:

Density & composition of lipoproteins

Two ways cholesterol is “packed” :

LDL:- Low Density Lipo-proteins

(“bad”)- a component of arterial

plaques that can lead to “blocked arteries”

HDL :- High Density Lipo-proteins

(“good”)- can help to clear LDL from

arterial walls

“Good” and “bad” cholesterolTrans & saturated fats (especially artificially

hydrogenated fats) in diet raise LDL levels

Trans: H on opposite sides

Mono-unsaturated fats (such as olive oil, canola oil) along with dietary fiber raise HDL levels

Cis: H on same side

ESSAY TITLES

1. Describe the role of the liver in (a) metabolism of carbohydrate (b) metabolism of protein and (c) metabolism of fat. [MAY, 1999]

2. Describe the role of the mammalian liver in

metabolism. [MAY, 2003]

3. Describe the human liver and its role in metabolism.

[SEP, 2007]