ALBIO5: STRUCTURE OF THE LIVER

The liver is the largest and most diversified organ within the body and contributes 5% of the total body mass with large blood supply.

It has below diaphragm and made up several lobes/lobule; cylindrical in shape C ~ 1mm in diameter.

Each lobule is filled with liver cells called hepatory tess radiating from the centre towards the periphery.

Liver  cells/hepatocytes are simple in structure, undifferentiated and all identical (uniform) in appearance; metabolically active; with large nuclei, prominent golgi apparatus and many mitochondria.

Blood supply to liver is from two sources:-

1. Hepatic artery; brings oxygenated blood from dorsal aorta.

1. Hepatic portal vein; brings blood rich in food materials from small intestines.

The liver sheds its products e.g. glucose, plasma protein, urea, cholesterol CO₂ into the hepatic artery and hepatic portal vein is mixed in spaces called sinusoids surrounded by hepatocytes. This increase 0₂ content of blood from hepatic portal vein, avoiding enough 02 to hepatocytes for their needs.

Hepatocytes secrete bile from the breakdown of blood into spaces called canaliculi and from these biles drains into bile ductiles which take it to the gall gladder.

The kupffer cells:-  

The liver cells specialized cells attached to the walls of the sinusoids called kupffer cells that are part of reticule entothelial system.

The liver performs four functions involved in protein metabolism

– Deamination                        – Transamination

– Urea formation                             – Plasma protein synthesis

Deamination

This body cannot store excess protein or amino acids. If more protein is eaten, that is used to build up muscle, or in cellular respiration the excess are deaminated together with amino acids not immediately required 4 protein synthesis or glyconeogenesis.

Deamination involves enzymatic removal of the amino (-NH2) group from the amino acid along with a hydrogen atom to ammonia.

Ammonia may be used for synthesis of certain amino acids, nitrogen bases like adenine and guanine or excreted.

The non nitrogenous parts of amino parts of amino acids (the organic acid) can be oxidized to carbohydrate (glucose) that can be used in respiration or turned to fat or glycogen and stored.

Urea formation/urea cycle/ornithine cycle.

Two molecules of NH₃ and 1 mole of CO₂ are used to produce one molecule of urea Co (NH₂) as follows:-  

One molecule of ammonia from deamination condenses with C02 and ornithine (a non essential amino acid) and looses one molecules of water to form citrulline.

Citrulline condenses with another molecule of ammonia, releasing one more molecule of water and forms orginine (a non essential amino acids).

Addition of a water molecule in presence of anginase enzyme to anginine hydrolyses it to one mole of onnithine and one mole of urea.

The ornithine regenerated is then used to repeat the cycle

The cycle is controlled by enzymes and ZATPs are needed to produce one mole of urea.

Transamination

Is the synthesis of amino acids deficient in diet by enzymatic transfer of the group from an amino acid to a carbohydrate in the form of a keto acid by exchanging radicals between the amino acid and a keto acid.

Example; formation of glutamic acid :-

Plasma protein production

The liver synthesizes plasma proteins e.g. albumin, globulins, hamamm and clothing factors like prothrombin, factor VIII .

5. Carbohydrate metabolism

The role of the liver in carbohydrate metabolism is to regulate blood glucose at the normal level of 90mg/100cm³ of blood.

All hexose sugar like galactose and fructose are converted to glucose by the liver and stored as glycogen.

When glucose levels rise above norm, the beta (5) cells of islets of longerhans of the pancreas are stimulated to secrete insulin that facilitate conversion of glucose to glycogen; a process known as glyconesis.

Glycogenesis process is summarized in the equation:-

Lactic acid produced by anaerobic respiration in skeletal muscle can be converted later into glucose and then glycogen in the liver in a pathway known as coricycle. This lactate mechanism is initiated by lactate – dehydrogena and proceeds as follows.

When glucose levels fall below norm, the oC (alpha) cells of lolets of langerhans of the pancreas are stimulated to secrete hormone glucagons that facilitate  conversion of glycogen to glucose in the liver; a process called glycogenolysis underline induces conversion of glycogen to glucose.

Glycogonolysis summarized in equation

Glucogenolysis can also occur under influence of hormone adrenaline.

When glycogen store in liver and musclwea iausted and no more glucose produced from them; glucose can be synthesized from non carbohydrate.

sources like amino acids, glycerol, fatty acids a process known as glynwogenesis.

Low levels of glucose also stimulates hypothalamus to release CRF (conticortrophic factor) which in turn releases adrenocorticotrophic hormone (ACTH) from anterion pituitary gland that leads to synthesis and release of gluccorticoid hormones cortisone and hydrocortisone. These stimulate glyconeogenesis also be increasing rate of synthesis of enzymes in liver which convert amine acids and glycerol into glucose.

Summary of carbohydrate metabolism.

Summary of regulation of sugar/glucose regulation when glucose level is higher than the normal 90mg/100cm³ of blood (hyperglycemia)

Beta (b) cells of islets of langenhans in pancrease (hyperglycemia)  are induced to produce insulin which:-

Facilitates convention of glucose to glycogen and stored in liver cells muscles (glycogenesis).

Glucose is converted to fat and stored in adipose cells.

1. Increases breakdown of sugar to CO₂ and H₂O during tissue respiration.
2. Inhibits glyconegenes (formation of glucose) from non carbohydrate sources like fats and proteins.

• Causes an increase in rate of absorption of glucose by muscle cells and liver.

Regulation when glucose levels drop below norm (hypoglycernia)

1. Alpha (j) cells of islets of langerhans in pancrease are included to reduce glucagons hormone that causes less insulin secretion.
2. Facilitate convernsion of glycogen to glucose (glyogenolysis) in liver and muscle cells.

• Reduces absorption of sugar by muscle cells and liver.

1. Increases (glyconeogenesis) and proteins (amino acid).
2. Adienaline may be released to facilitate glycogenolysis in the liver especially during sudden stress, llike when one is frightened or excitement.

When the glycogen stores are over and no more glucose released from them; another hormone called cortisone secretes secretes from adrenal glands to promote glyconecogenesis

Effect of a malfunctioning pancreas

When the pancreas fails to function properly, it will not perform its exocrine and endocrine roles in the body.

Exocrine roles:

The pancreas would not secrete pancreatic juice which is digestive and contains the enzymes; pancreatic amylase and pancreatic lipase, inactive trypsinogen and chymotrypsinogen.

Hence no hydrolysis/digestion of starch to maltose. Lipids to fatty acids and glycerol and of proteins to polypetides.

Endocrine roles

The j-cells of islets of langerhans will not secrete glucagons; hence low blood sugar cannot be raised; because glycogenolysis cannot occur, person then suffers from a hypoglycemia hypoglycaemia.

The b-cells of islets of langerhans will not secrete insulin, so blood sugar level may rise above norm and could be excreted in urine a condition known as glycosisria and the person is said to suffer from diabetes mellitus; because the convernsion and storage of excess glucose to glycogen (glycogenesis) in the liver will not take place;

Also increased uptake and metabolism of glucose by liver and muscle cells will not occur.

And synthesis of fat and proteins from excess glucose will take place.

The state of having glucose level above norm (90mg/100cm3 of blood) is known as hyperglycemia hyperglycemia.

Types of diabetes mellitus

There are two forms with different causes.

1. Type I diabetes mellitus
2. type II diabetes mellitus.

Type I diabetes mellitus

• Also called insulin dependent diabetes on jurenile onset diabetes.
• Usually occurs suddenly in childhood.
• It is an autoimmune disease ie cells from immune system attack b-cells in islets of langerhans and n insulin secreted.
• Hyperglycemia occurs in the kidneys though healthy cannot reabsorb the glucose resultinf n glucose bneing in urine (glycosuria).
• Symptoms include dehydration, loss of weight and lethargy.
• Sfferens have the disease for the rest of their lives.

Treatment

Insulin injections matches with amount of carbohydrate eaten and exercise taken.

Insulin cannot be taken orally because being a protein, it would be digested in the alimentary canal.

Type II diabetes mellitus

• Also called insulin independent diabetes on late onset diabetes.
• Usually occurs later in life.
• Represents 90% of all cases of diabetes.
• Insulin is still produced but caused by failure of cells to respond to insulin.
• Colucose uptake by cells becomes erratic.
• Symptoms are similar to those for type I but are mild in comparison.
• It is linked with high fat diests and obesity/overweight (especially in well communities).

Treatment

• Dietary control including low carbohydrate intake and exercise to regulate glucose in the body.

NB

At times, late on diabetes in adults could be due to take place of insulin.

6. The liver also carries out fat metabolism, regulating lipids by synthesizing them or eliminating them are required (give details).
7. Detoxication eg of HO O2, alcohol, poison etc. (Detoxification).
8. Regulates and stores vitamins A, B, B_12.
9. Regulates and stores inorganic elements K, Fe, Cu.
10. Regulates temperature/produces heat.
11. Stores blood/reservoir for blood.
12. Produces bile.
13. Removes used haemoglobin and destroys old R.B.C’s
14. Inactivation of hormone after exacting their effects.
15. Produce R.B.C’s in foetus only but not adult.
16. Formation and elimination of cholesterol. Look 4 for more functions of liver.