Functions of Human Liver (With Diagram) | Organs | Biology

Liver is an essential organ of the body. Its functions are numerous which are briefly summarised below:

1. In Connection with Blood and Circulation:

i. R.B.C. formation—in foetal life.

ii. R.B.C. destruction—in adult life.

iii. Storehouse of blood and regulates blood volume.

iv. Relation with blood clotting.

a. Manufactures prothrombin (with the help of vitamin K) and fibrinogen and thus essential for clot­ting.

b. Mast cells form heparin and prevent intravascular clotting.

v. Related to activity of its R.E. system in immune mechanism.

vi. It transfers blood from portal to systemic circulation.

vii. Manufactures all plasma proteins.

viii. Stores iron, haematinic factor also known as vitamin B₁₂ and copper, and thus helps in the formation of red cells and haemoglobin.

ix. Hepatic and Portal Circulation –  The total flow of blood in the liver through both hepatic artery and portal vein is about 1.5 litre/minute. 20-30% of which is carried by the hepatic artery and 100% saturated with O₂ whereas the remaining is carried by portal vein which is 80-90% saturated with O₂. Portal venous blood is derived mainly (60%) from superior mesenteric vein and remaining from splenic vein.

The bloods of two streams are well mixed in man before they are supplied to the cell and thereby every cell receives the same blood. The pressure in the portal system is normally between 5 and 13 mm of Hg. Due to high pressure in arterial blood of hepatic sinusoids, the portal blood mixes with it freely. The hepatic vein formed from the central vein in which hepatic venous pressure is about 6 mm of Hg and normally 60% is saturated with O₂.

In vascular components of the liver there are sphincters which regulate local contributions of hepatic artery, portal vein, total liver blood flow and the capacity of total venous bed. Thus the liver can accommodate blood up to one-third of the total blood volume.

The liver produces 75 ml of lymph per minute and its protein content is 90% of that of plasma. Through hepatic lymphatics, 40% of the total plasma protein is returned to the blood in each 24-hour.

2. Manufactures Bile:

Bile is secreted continuously from the liver cells and stored in the gall-bladder. Bile contains water (11.14%), total solid (5.18%), mucin and pigments (3.42%), neutral fat (0.37%), fatty acids (0.97%), phospholipids (0.2%), cholesterol (0.63%) and inorganic ions (0.85%).

Cholesterol is synthesised in the liver from active acetate. Cholesterol is also excreted from the liver. Bile acids—cholic acid, deoxycholic acid and lithocholic acid have been considered to be the derivatives of cholanic acid and formed in the liver.

The bile acids in conjugation with glycine and taurine, form the compounds—glycocholic acid and taurocholic acid respectively. Bile salts are the Na-salts of taurocholic acid and glycocholic acid. Bile salts have got important functions in absorption of fats and also for the emulsification of fats with the concurrent production a great surface area to enable lipase and other enzymes to act more efficiently.

Bile pigments are the biliverdin and bilirubin. These are the excretory products of haemoglobin of broken down R.B.C. and are formed in the R.E. system in the various parts of the body.

Bone-marrow, liver and spleen have been considered to be the site of formation of the bile pigments.

3. Relation with Carbohydrate Metabolism:

i. Converts non-glucose monosaccharides into glucose (and glycogen).

ii. Converts lactic acid, pyruvic acid and glycerol into glucose and also glycogen.

iii. Stores carbohydrate in the form of glycogen (glycogenesis) and when blood sugar tends to be low, it mobilises glycogen (glycogenloysis).

iv. Takes an important part in blood sugar regulation. (Figs 10.124, 10.125 10.126, 10.127 & 10.129)

v. It is the seat of neoglucogenesis.

vi. Manufactures fats from carbohydrates, etc.

vii. Glucose is metabolised here through TCA cycle and other alternative pathway (HMO shunt).

viii. Clucurorric acid is formed from uridine diphosphate glucose (UDPG) which plays an important role in the conjugation of bilirubin and other substances (Fig. 10.126).

ix. Alcohol metabolism. (Fig. 10.121). The liver is the main seat of alcohol metabolism. A zinc-containing enzyme, alcohol dehydrogenase catabolises acetaldehyde. A coenzyme acetaldehyde dehydrogenase converts acetaldehyde to acetyl CoA. Acetaldehyde can be further catabolised to acetate. Acetate may be oxidized to CO₂ and H₂O or converted to other biochemical compounds including fatty acids through TCA cycle.

When alcohol is converted to acetaldehyde and then to acetyl CoA, NAD acts as a cofactor, i.e., hydrogen acceptor. ATP, generated by the oxidation of NADH through electron transport chain (ETC) of oxidation, provides energy for the synthesis of fatty acids.

The reduction of activity of TCA cycle substrates is due to decreased fatty acid oxidation. On the other hand, NADH + H⁺, being hydrogen carrier, is utilized for the conversion of pyruvate to lactate and for this reason alcohol raises blood lactate level. It is postulated that this, mechanism explains post-alcoholic hypoglycaemia.

Hepatic micorsomes help in the esterification of fatty acids to triglycerides rather than phospholipids. The direct effect of alcohol may be alcoholic fatty liver which is the cause of increased hepatic fatty acid synthesis as well as decreased hepatic hepatic acid oxidation.

4. Relation with Fat Metabolism (Figs 10.128 & 10.129):

i. It stores fats. Liver contains about 3% of fat (with mixed diet).

ii. It helps in the oxidation of fat, releasing energy in the form of ATP.

iii. Site of synthesis of cholesterol from acetate.

iv. Synthesises phospholipids.

v. Synthesises fats from carbohydrates and proteins.

vi. It is the seat of ketone body formation.

vii. Unused free fatty acid (FFA) released from fat depot, is converted to triglycerides and other lipids to meet energy requirement.

viii. Glycerol is oxidized here via the pathways of carbohydrate metabolism.

ix. In a carbohydrate deficiency, the fat metabolism in the liver is increased and fat is partially converted to glucose or glycogen.

x. Fat-soluble vitamins, e.g., A, D, E, K, are stored here.

5. Relation with Protein Metabolism:

i. It is the seat of specific dynamic action of protein.

ii. Chief seat of deamination.

iii. Main seat of urea and uric acid formation.

iv. Synthesis of some amino acids takes place here.

v. Plasma proteins are manufactured here except immunoglobulin.

vi. Coagulation factors, in addition to fibrinogen and prothrombin, are manufactured here.

vii. It is the seat of nitrogen metabolism as evident from deamination process, urea synthesis, etc.

6. Hormone Metabolism:

i. Reduces the circulating adrenal cortical and sex hormones by degradation and conjugation. Steroid hor­mones like oestrogen, Cortisol, testosterone, etc. are insoluble and solubility is increased and made excretable after being conjugated with glucuronic acid and sulphuric acid in the liver.

Normally the liver inactivates adrenocortical hormones by reduction of the 4-3-ketonic group with the formation of tetrahydroderivatives, which are then either oxidized to the 17-ketosteroids or the C-20 ketone. In hepatocel­lular disease there is defect at the stage of reduction of the 4-3 ketone group and not in its conjugation.

ii. The liver normally extracts about 97% of aldosterone delivered and is converted into both acid hydrolysable conjugate (AHC) and to tetrahydroaldosterone. Extra-hepatic tissue also metabolises certain amount into AHC. In the liver disease the utilisation by extra-hepatic tissue is increased.

iii. Oestrogens are inactivated by the liver. The enzyme 16-a-hydroxylase is concerned in conversion of oestrone to 16-hydroxyoestrone, the precursor of oestriol. In patients with severe liver disease, the ac­tivity of this enzyme is impaired and oestradiol excretion is increased in association with decreased excretion of oestriol.

iv. The liver cells can clear testosterone from the blood rapidly through conjugation. In liver disease, though the testosterone is removed from the blood but excretion of 17-ketosteroids in the urine is reduced.

v. Inactivation of insulin, glucagon, antidiuretic hormone (ADH), and anterior pituitary trophic hormones, etc., occur here.

7. Relation with Vitamins:

i. Manufactures prothrombin with the help of vitamin K.

ii. It forms vitamin A from carotene and stores vitamins A and D.

iii. Chronic liver disease is always associated with folic acid deficiency.

It is known that the liver converts folate to its active form—tetrahydro folate. Tacrahydrofolate is the storage form of folic acid. In liver disease, this enzymatic transformation of tetrahydrofolate becomes impossible and thus folic acid is excreted in the urine.

iv. The liver is the principal storage organ for vitamin B₁₂ and in condition of hepto-cellular disease. The uptake of vitamin B₁₂ by the liver tissue is decreased.

8. Excretory Functions:

i. Certain heavy metals are temporarily fixed by the liver cells which are then excreted in the bile.

ii. Various toxins, bacteria and drugs are excreted through bile.

iii. Cholesterol and bile pigments are excreted in the bile.

9. Detoxicating and Protective Functions:

The liver is the site of detoxication of different toxic substances either produced in the body or taken along with food. Detoxication is the process by which toxic substances are rapidly made excretable through different biochemical changes. This is done by the process of oxidation, hydrolysis, reduction and conjugation. Drugs are also made excretable by the liver enzymes. The enzymes for the above processes are bound to hepatic microsomes.

Detoxication processes of the drugs and other toxic substances are as follows:

i. Oxidation:

Drugs phenylbutazone and hexobarbital are detoxified mainly in the liver cells. It requires NA- DPH, O₂ and microsomal enzymes. Phenylbutazone is oxidised to oxiphenbutazone and the hexobarbi­tal is oxidised to an inactive substance (Fig. 10.130). Besides these, a large amount of foreign substances are metabolised in the body by oxidation. Many primary aliphatic amines are detoxified in the liver with the formation of corresponding acid and the nitrogen is converted into urea according to the gen­eral reaction.

The sulphur of a good number of organic sulphur compounds is oxidised to sulphate to varying degrees and the sulphate is excreted in organic or inorganic form.

ii. Hydrolysis:

Pethidine is hydrolysed by microsomal enzymes to inactive metabolite (Fig. 10.131). The drug procaine is also rapidly hydrolysed into para-aminobenzoic acid and diethylamino ethanol.

iv. Reduction:

This process requires NADH or NADPH as hydrogen donor and also flavoprotein enzyme. Chloramphenicol or Chloromycetin is detoxified by this process into its inactive by-product (Fig. 10.132).

Many nitrocompounds are also detoxified by this process. Picric acid is reduced into picramic acid. But both the acids are excreted into the urine. Chloral hydrate is partly reduced into trichloroethanol.

This reduction process is also employed for the conversion of:

i. S—S—linkages to -SH groups,

ii. Azo compounds to amines, e.g., para-dimethylaminoazobenzene (butter yellow), and para-aminophenol Conjugation: By this process a good number of toxic substances are detoxified and eliminated from the system.

These are:

(a) Bilirubin as glucuronide,

(b) Phenol as glucuronide or phenyl sulphuric acid, and

(c) Benzoic acid in conjugation with glycine as hippuric acid (Fig. 10.133), and also with glucuronic acid as glucuronide,

(d) Phenylacetic acid in conjugation with glycine as phenylaceturic acid and in conjugation with glutamine as phenylacetyl glutamine,

(e) Bromobenzene in conjugation with acetylated cysteine as para-bromophenyl mercapturic acid,

(f) Sulphanilamide in conjugation with acetyl CoA (through acetylation) as para-N-acetyl benzene sulphonamide (Fig. 10.134).

v. Takes Part in Heat Regulation:

The liver produces a large amount of heat and takes part in heat regulation.

vi. It is also responsible for the liberation of a depressor principle.

It is the storehouse of Fe, fat-soluble vitamins, glycogen, labile protein, fat, etc. Different metabolic functions of the liver have been presented Fig. 10.129.