Liver and Gallbladder Functions Properties Notes

Functional Anatomy Of Liver And Biliary System

The liver is a dual organ having both secretory and excretory functions. It is the largest gland in the body weighing about 1.5 kg in man. It is located in the upper and right side of the abdominal cavity immediately beneath the diaphragm.

Liver:

1. Hepatic Lobes: The liver is made up of many lobes called hepatic lobes. Each lobe consists of many lobules called hepatic lobules.
2. Hepatic Lobules: The hepatic lobule is the structural and functional unit of the liver. There are about 50,000-100,000 lobules in the liver. The lobule is a honeycomb-like structure and it is made up of liver cells called hepatocytes.
3.  Hepatocytes and Hepatic Plates:
   1. Hepatocytes are arranged in columns which form the hepatic plates. Each plate is made up of two columns of cells. In between the two columns of each plate, lies a bile canaliculus.
   2. In between the neighboring plates, a blood space called a sinusoid is present.
4. Portal Triads
   • Each lobule is surrounded by many portal triads. Each portal triad consists of three vessels:
     • A branch of the hepatic artery
     • A branch of the portal vein
     •  A tributary of bile duct

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• The branches of the hepatic artery and portal vein open into the sinusoid. The Sinusoid opens into the central vein. Central vein empties into the hepatic vein. The Sinusoid is lined by the endothelial cells. In between the endothelial cells, some special macrophages called Kupffer’s cells are present.
• Bile is secreted by hepatic cells and emptied into the bile canaliculus. From the canaliculus, the bile enters the tributary of the bile duct. The tributaries of the bile duct from the canaliculi of neighboring lobules unite to form small bile ducts. These small bile ducts join together and finally form left and right hepatic ducts which emerge out of the liver.

Biliary System:

• The biliary system is also known as the extrahepatic biliary apparatus. It is formed by the gallbladder and the extrahepatic bile ducts (bile ducts outside the liver). The right and left hepatic bile ducts which come out of the liver join to form a common hepatic duct. It unites with the cystic duct from the gallbladder to form a common bile duct.
• Right and left hepatic bile ducts, common hepatic duct, cystic duct, and common bile duct are having similar structures. The common bile duct unites with the pancreatic duct to form the common hepatopancreatic duct or ampulla of Vater which opens into the duodenum.
• There is a sphincter called the sphincter of Oddi at the lower part of the common bile duct before it joins the pancreatic duct. It is formed by smooth muscle fibers of the common bile duct. It is normally kept closed; so the bile secreted from the liver enters the gallbladder where it is stored. Upon appropriate stimulation, the sphincter opens and allows the flow of bile from the gallbladder into the intestine.

Blood Supply To Liver

The liver receives blood from two sources namely the hepatic artery and portal vein.

Hepatic Artery: The hepatic artery arises directly from the aorta and supplies pure arterial blood to the liver. After entering the liver, the hepatic artery divides into many branches. Each branch enters a portal triad.

Portal Vein:

• The portal vein is formed by the superior mesenteric vein and splenic vein. It brings deoxygenated blood from the stomach, intestine, spleen, and pancreas. The portal blood is rich in monosaccharides and amino acids. It also contains bile salts, bilirubin, urobilinogen, and Gl hormones. However, the oxygen content is less in portal blood.
• The flow of blood from the intestine to the liver through the portal vein is known as enterohepatic circulation.
• The blood from the hepatic artery mixes with blood from the portal vein in the hepatic sinusoids. The hepatic cells obtain oxygen and nutrients from the sinusoid.

Hepatic Vein: The substances synthesized by hepatic cells, the waste products, and carbon dioxide are discharged into sinusoids. The sinusoids drain them into the central vein of the lobule. The central veins from many lobules unite to form bigger veins which ultimately form hepatic veins (right and left) which open into the inferior vena cava.

Properties And Composition Of Bile

Bile is a golden-yellow or greenish fluid. It enters the digestive tract along with pancreatic juice through the common opening called the ampulla of Vater.

• Properties Of Bile:
  • Volume              : 800-1200 mL/day
  • Reaction            : Alkaline
  • pH                      : 8-8.6
  • Specific gravity  : 1.010-1.011
• Composition Of Bile: Bile contains of 97.6% of water and 2.4% of solids. Solids include organic and inorganic substances.

Secretion Of Bile

• Bile is secreted by hepatocytes. The initial bile secreted by hepatocytes contains a large number of bile acids, bile pigments, cholesterol, lecithin, and fatty acids. From hepatocytes, the file is released into canaliculi.
• From here, the bile enters the common hepatic duct by passing through small ducts and hepatic ducts. From the common hepatic duct, bile is diverted either directly into the intestine or into the gallbladder where it is stored.
• Sodium, bicarbonate, and water are added to bile when it passes through the ducts. These substances are secreted by the epithelial cells of the ducts. The addition of sodium, bicarbonate, and water increases the total quantity of bile.

Storage Of Bile

Most of the bile from the liver enters the gallbladder where it is stored. It is released from the gallbladder into the intestine whenever it is required. When bile is stored in the gallbladder, it undergoes many changes both in quality and quantity such as:

1. A large amount of water and electrolytes (except calcium and potassium) are absorbed resulting in high concentrations of bile salts, bile pigments, cholesterol, fatty acids, and lecithin
2. The pH and specific gravity of bile are altered in the gallbladder
3. Some amount of mucin is added to bile.

Bile Salts

Bile salts are the sodium and potassium salts of bile acids, which are conjugated with glycine or taurine.

Formation Of Bile Salts:

• Bile salts are formed from bile acids. There are two primary bile acids in humans namely cholic acid and chenodeoxycholic acid which are formed in the liver and enter the intestine through bile. Due to the bacterial action in the intestine, the primary bile acids are converted into secondary bile acids:
  • Cholic acid → deoxycholic acid
  • Chenodeoxycholic acid → lithocholic acid
• Secondary bile acids from the intestine are transported back to the liver through enterohepatic circulation. In the liver, the secondary bile acids are conjugated with glycine (amino acid) or taurin (a derivative of amino acid) and form conjugated bile acids namely glycocholic acid and taurocholic acids.
• These bile acids combine with sodium or potassium ions to form salts, sodium or potassium glycocholate, and sodium or potassium taurocholate.

Enterohepatic Circulation Of Bile Salts:

• Enterohepatic circulation is the transport of substances from the small intestine to the liver through the portal vein. About 90-95% of bile salts from the intestine are transported to the liver through enterohepatic circulation.
• The remaining 5-10% of the bile salts enter the large intestine. Here the bile salts are converted into deoxycholate and lithocholate which are excreted in feces.

Functions Of Bile Salts:

The bile salts are required for digestion and absorption of fats in the intestine. The functions of bile salts are:

1. Emulsification of Fats:

• Emulsification is the process by which the fat globules are broken down into minute droplets and made in the form of a milky fluid called emulsion. Fats are made into an emulsion in the small intestine by the action of bile salts.
• Emulsification increases the surface area of these lipids making them much easier to digest. Unemulsified fat usually passes through the intestines and then it is eliminated in feces.
• The lipolytic enzymes of the Gl tract cannot digest the fats directly because the fats are insoluble in water due to the surface tension. The bile salts emulsify the fat by reducing the surface tension of the fats due to their detergent action.
• Because of the reduction in surface tension, the lipid granules are broken into minute particles which can be easily digested by lipolytic enzymes. The emulsification of fats by bile salts needs the presence of lecithin from bile.

2. Absorption of Fats: Bile salts help in the absorption of digested fats from the intestine into the blood. The bile salts combine with fats and make complexes of fats called micelles. The fats in the form of micelles can be absorbed easily.

3. Choleretic Action: Bile salts stimulate the secretion of bile from the liver. This action is called choleretic action.

4. Cholagogue Action: Cholagogue is an agent, which increases the release of bile from the gallbladder into the intestine by contraction of the gallbladder. Bile salts act as cholagogues indirectly by stimulating the secretion of the hormone cholecystokinin. This hormone causes contraction of the gallbladder resulting in the release of bile.

5. Laxative Action: Laxative is an agent which induces defecation. Bile salts act as laxatives by stimulating peristaltic movements of the intestine.

6. Prevention of Gallstone Formation: Bile salts prevent the formation of gallstones by keeping the cholesterol and lecithin in solution. In the absence of bile salts, cholesterol precipitates along with lecithin and forms gallstone.

Bile Pigments

Bile pigments are the excretory products in bile. Bilirubin and biliverdin are the two bile pigments and bilirubin is the major bile pigment in human beings. The bile pigments are formed during the breakdown of hemoglobin, which is released from the destroyed RBCs in the reticuloendothelial system.

Formation And Excretion Of Bile Pigments: Stages of formation and circulation of bile pigments:

• The senile erythrocytes are destroyed in reticuloendothelial system and hemoglobin is released from them
• The hemoglobin is broken into globin and heme
• Heme is split into iron and the pigment biliverdin
• The Iron goes to the iron pool and is reused
• The first formed pigment biliverdin is reduced to bilirubin
• The bilirubin is released into the blood from reties :ioervdothelial cells
• In the blood, bilirubin is transported by the plasma protein, albumin. The bilirubin circulating in the blood is called free bilirubin or unconjugated bilirubin
• Within a few hours after entering the circulation, the free bilirubin is taken up by the liver cells
• In the liver, it is conjugated with glucuronic acid to form conjugated bilirubin
• Conjugated bilirubin is then excreted into the intestine through bile.

Fate Of Conjugated Bilirubin: Stages of excretion of conjugated bilirubin:

• In the intestine, 50% of the conjugated bilirubin is converted into urobilinogen by intestinal bacteria. First, the conjugated bilirubin is deconjugated into free bilirubin which is later reduced into urobilinogen.
• The remaining 50% of conjugated bilirubin from the intestine is absorbed into the blood and enters the liver through the portal vein (enterohepatic circulation). From the liver, it is re-excreted in bile
• Most of the urobilinogen from the intestine enters the liver via enterohepatic circulation. Later, it is re-excreted through the bile
• Converted into urobilin by oxidation
• Some of the urobilinogen is excreted in feces as stercobilinogen. In feces, stercobilinogen is oxidized to stercobilin.

Normal Plasma Levels Of Bilirubin: The normal bilirubin (Total bilirubin) content in plasma is 0.5-1.5 mg/dL. When it exceeds 1mg/dL, the condition is called hyperbilirubinemia. When it exceeds 2 mg/dL, jaundice occurs.

Functions Of Bile

Most of the functions of bile are due to the bile salts.

1. Excretory Functions: Bile pigments are the major excretory products of the bile. The other substances excreted in bile are:

• Heavy metals like copper and iron
• Some bacteria like typhoid bacteria
• Some toxins
• Cholesterol
• Lecithin
• Alkaline phosphatase.

2. Laxative Action: Bile salts act as laxatives (see above).

3. Antiseptic Action: Bile inhibits the growth of certain bacteria in the lumen of the intestine by its natural detergent action.

4. Choleretic Action: Bile salts have a choleretic action (see above).

5. Maintenance Of Ph In Gastrointestinal Tract: As the bile is highly alkaline, it neutralizes acid chyme which enters the intestine from the stomach. Thus, an optimum pH is maintained for the action of digestive enzymes.

6. Lubrication Function: The mucin in bile acts as a lubricant for the chyme in the intestine.

7. Cholagogue Action: Bile salts act as cholagogues (see above).

Functions Of Liver

The liver is the largest gland and one of the vital organs of the body. It performs many vital metabolic and homeo¬static functions, which are summarized below.

1. Metabolic Function: The liver is the organ where maximum metabolic reactions are carried out. It plays an important role in energy metabolism. Metabolism of carbohydrates, proteins, fats, vitamins, and many hormones is carried out in the liver.

2. Storage Function: Many substances like glycogen, amino acids, iron, folic acid, and vitamins A, B12, and D are stored in the liver.

3. Synthetic Function: The liver produces glucose by gluconeogenesis. It synthesizes all the plasma proteins and other proteins (except immunoglobulins) such as clotting factors, complement factors, and hormone-binding proteins. It also synthesizes steroids, somatomedin, and heparin.

4. Secretion Of Bile: Liver secretes bile, which contains bile salts, bile pigments, cholesterol, fatty acids, and lecithin.
The functions of bile are mainly due to the bile salts. The bile salts are required for digestion and absorption of fats in the intestine. Bile helps to carry away waste products and break down fats, which are excreted through feces or urine.

5. Excretory Function: The liver excretes cholesterol, bile pigments, heavy metals (like lead, arsenic, and bismuth), toxins, bacteria and viruses (like that of yellow fever) through bile:

6. Heat Production: Enormous amount of heat is produced in the liver because of the metabolic reactions. The liver is the organ where maximum heat is produced.

7. Hemopoietic Function: In the fetus (hepatic stage), the liver produces the blood cells \ (Chapter 10). It stores vitamin B12 necessary for erythropoiesis and iron necessary for the synthesis of hemoglobin. The liver produces thrombopoietin which promotes the production of thrombocytes.

8. Hemolytic Function: The senile RBCs after the lifespan of 120 days are destroyed by reticuloendothelial cells (Kupffer’s cells) of the liver.

9. Inactivation Of Hormones And Drugs: Liver catabolizes the hormones such as growth hormone, parathormone, cortisol, insulin, glucagon, and estrogen. It also inactivates drugs, particularly fat-soluble drugs. The fat-soluble drugs are converted into water-soluble substances, which are excreted through bile or urine.

10. Defensive And Detoxification Functions:

• The reticuloendothelial cells (Kupffer’s cells) of the liver play an important role in the defense of the body. The liver is also involved in the detoxification of foreign bodies.
• The foreign bodies such as bacteria or antigens are swallowed and digested by reticuloendothelial cells of the liver by means of phagocytosis
• The reticuloendothelial cells of the liver are also involved in the production of some substances like interleukins and tumor necrosis factors, which acti¬vate the immune system of the body
• Liver cells are involved in the removal of toxic properties of various harmful substances. The removal of toxic properties of the harmful agent is known as detoxification. The detoxification in the liver occurs in two ways:
• Total destruction of the substances by means of metabolic degradation
• Conversion of toxic substances into nontoxic materials by means of conjugation with glucuronic acid or sulfates.

Gallbladder

The bile secreted from the liver is stored in the gallbladder. The capacity of the gallbladder is approximately 50 mL. The gallbladder is not essential for life. The removal of gallbladder (cholecystectomy) is often done in patients suffering from gallbladder dysfunction. After cholecystectomy, patients do not suffer from any major disadvantage. In some species, gallbladder is absent.

Functions Of Gallbladder:

The major functions of the gallbladder are the storage and concentration of bile.

1. Storage of Bile: Bile is continuously secreted from the liver. But it is released into the intestine only intermittently and most of the bile is stored in the gallbladder till it is required.
2. Concentration of Bile: Bile Is concentrated while it is stored in the gallbladder. The mucosa of the gallbladder rapidly reabsorbs water and eieciroiyu;? except for calcium and potassium. But the bile pigments, cholesterol and lecithin are not rc.ilv-.c!bfe.d So, the concentration of these substances in Asia increases 5 to 10 times.
3. Alteration of pH of Bile: The pH of bile decreases from 8-8.6 to 7-7.6 and it becomes less alkaline when it is stored in the gallbladder.
4. Secretion of Mucin: Gallbladder secretes mucin, which acts as a lubricant for the movement of chyme in the intestine.
5. Maintenance of Pressure in Biliary System: Due to the concentrating capacity, the gallbladder maintains a pressure of about 7 cm H20 in the biliary system. This pressure in the biliary system is essential for the release of bile into the intestine.

Filling And Emptying Of Gallbladder:

• Usually, the sphincter of Oddi is closed during fasting and the pressure in the biliary system is only 7 cm H20. Because of this pressure, the bile from the liver enters the gallbladder.
• While taking food or when chyme enters the intestine, the gallbladder contracts along with relaxation of the sphincter of Oddi. Now, the pressure increases to about 20 cm H20. Because of the increase in pressure, the bile from the gallbladder enters the intestine. Contraction of the gallbladder is influenced by neural and hormonal factors.
  • Neural Factor: Stimulation of the parasympathetic nerve (vagus) causes the contraction of the gallbladder by releasing acetylcholine. The vagal stimulation occurs during the cephalic phase and gastric phase of gastric secretion.
  • Hormonal Factor: When a fatty chyme enters the intestine from the stomach, the intestine secretes cholecystokinin which causes contraction of the gallbladder.

Regulation Of Bile Secretion

Bile secretion is a continuous process though the amount may be less during fasting. It increases three hours after meals. The Secretion of bile from the liver and release of bile from the gallbladder are influenced by some chemical factors which are categorized into three groups:

1. Choleretics
2. Cholagogue
3. Hydrocholeretic agents.

1. Choleretics: Substances, which increase the secretion of bile from the liver, are known as choleretics. The effective choleretic agents are

• Acetylcholine
• Secretin
• Cholecystokinin
• Acid chyme in intestine
• Bile salts.

2. Cholagogues: Cholagogue is an agent, which increases the release of bile from the gallbladder into the intestine. It does not influence the secretion of bile in the liver. The release of bile into the intestine is achieved by causing contraction of the gallbladder. The common cholagogues are:

• Bile salts
• Calcium
• Fatty acids
• Amino acids
• Inorganic acids.

All these substances stimulate the secretion of cholecystokinin, which in turn causes contraction of the gallbladder and flow of bile into the intestine.

3. Hydrocholeretic Agents: Hydrocholeretic agent is a substance, which causes the secretion of bile from the liver with a large amount of water and less amount of solids. Hydrochloric acid is a hydrocholeretic agent.

Applied Physiology

Jaundice Or Icterus:

• Jaundice or icterus is a condition characterized by the yellow coloration of the skin, mucous membrane, and deeper tissues due to increased bilirubin level in blood. The word jaundice is derived from the French word “jaune meaning yellow.
• The normal serum bilirubin level is 0.5-1.5 rng/dL Jaundice occurs when the bilirubin level exceeds 2 mg/dL

Types of Jaundice: Jaundice is classified into three types:

1. Prehepatic or hemolytic jaundice
2. Hepatic or hepatocellular jaundice
3. Posthepatic or obstructive jaundice.

1. Prehepatic or Hemolytic Jaundice:

• Hemolytic jaundice is the type of jaundice that occurs because of excessive destruction of RBCs resulting in increased blood levels of free (unconjugated) bilirubin. In this condition the function of the liver is normal. But the quantity of bilirubin increases enormously. The liver cells cannot excrete that much bilirubin rapidly. So, it accumulates in the blood resulting in jaundice.
• The formation of urobilinogen also increases resulting in the excretion of more amount of urobilinogen in urine.

Hemolytic Jaundice Causes: Any condition that causes hemolytic anemia can lead to hemolytic jaundice. The common causes of hemolytic jaundice are:

• Liver failure
• Renal disorder
• Hypersplenism
• Burns
• Infections such as malaria
• Hemoglobin abnormalities such as sickle cell anemia or thalassemia
• Drugs or chemical substances causing red cell damage
• Autoimmune diseases.

2. Hepatic or Hepatocellular or Cholestatic Jaundice: This is the type of jaundice that occurs due to the damage of hepatic cells. Because of the damage, the conjugated bilirubin from liver cannot be excreted and it returns to the blood.

Hepatic Causes:

• Infection (infective jaundice) by virus resulting in hepatitis (viral hepatitis)
• Alcoholic hepatitis
• Cirrhosis of liver
• Exposure to toxic materials.

3. Posthepatic or Obstructive or Extrahepatic Jaundice: This type of jaundice occurs because of the obstruction of bile flow at any level of the biliary system. The bile cannot be excreted into the small intestine. So, bile salts and bile pigments enter the circulation. The blood contains more amount of conjugated bilirubin.

Posthepatic Causes:

• Gallstones
• Cancer of the biliary system or pancreas.

Hepatitis:

Hepatitis is the liver damage caused by many agents. It is characterized by swelling and inadequate functioning of the liver. Hepatitis may be acute or chronic. In severe conditions, it may lead to liver failure and death.

Hepatitis Causes and Types:

• Viral infection – Viral hepatitis (see below)
• Bacterial infections like leptospirosis and Q fever
• Excess consumption of alcohol
• Excess administration of drugs like paracetamol
• Poisons like carbon tetrachloride and aflatoxin
• Wilson’s disease
• Circulatory insufficiency
• Inheritance from mother during parturition.

Viral Hepatitis: Viral hepatitis is the type of hepatitis caused by viruses. It is caused by two types of viruses, hepatitis A and hepatitis B.

Viral Hepatitis Causes: Viral hepatitis is caused by

• Mainly by intake of water and food contaminated with the hepatitis virus
• Sharing needles with infected persons
• Accidental prick by an infected needle
• Having unprotected sex with infected persons
• Inheritance from mother during parturition
• Blood transfusion from infected donors.

Hepatitis caused by hepatitis B virus is more common and considered more serious because it may lead to cirrhosis and cancer of the liver.

Features of Hepatitis:

• Fever
• Nausea
• Vomiting, diarrhea, and loss of appetite
• Headache and weakness
• In addition, chronic hepatitis is characterized by
  • Stomach pain
  • Paleness of skin
  • Dark-colored urine and pale stool
  • Jaundice
  • Personality changes.

Cirrhosis Of the Liver:

Cirrhosis of the liver refers to inflammation and damage of the parenchyma of the liver. It results in the degeneration of hepatic cells and dysfunction of the liver.

Cirrhosis Of Liver Causes:

1. Infection
2. Retention of bile in the liver due to obstruction of ducts of the biliary system
3. Enlargement of the liver due to intoxication
4. Inflammation around the liver – perihepatitis
5. Infiltration of fat in hepatic cells.

Cirrhosis Of Liver Features:

1. Fever, nausea and vomiting
2. Jaundice
3. Increased heart rate and cardiac output
4. Portal hypertension
5. Muscular weakness and wasting of muscles
6. Drowsiness
7. Lack of concentration and confused state of mind
8. Coma in advanced stages.

Gallstones:

Gallstones Definitions: A gallstone is a solid crystal deposit that is formed by cholesterol, calcium ions, and bile pigments in the gallbladder or bile duct. Cholelithiasis is the presence of gallstones in the gallbladder. Choledocholithiasis is the presence of gallstones in the bile ducts.

Formation of Gallstones:

• Normally, cholesterol present in the bile combines with bile salts and lecithin, which make the cholesterol soluble in water. Under some abnormal conditions, this water-soluble cholesterol precipitates resulting in the formation of gallstones.
• Initially, a small quantity of cholesterol begins to precipitate forming many small crystals of cholesterol in the mucosa of the gallbladder. This stimulates further formation of crystals, and the crystals grow larger and larger. Then, bile pigments and calcium are attached to these crystals resulting in the formation of gallstones.

Causes for Gallstone Formation:

1. Reduction in bile salts and/or lecithin
2. Excess of cholesterol
3. Disturbed cholesterol metabolism
4. Excess of calcium ions due to increased concentration of bile
5. Damage or infection of gallbladder epithelium. It alters the absorptive function of the mucous membrane of the gallbladder. Sometimes, there is excessive absorption of water or even bile salts leading to increased concentrations of cholesterol, bile pigments, and calcium ions
6. Obstruction of bile flow from the gallbladder.

Diagnosis of Gallstone: The presence of gallstone is diagnosed by ultrasound scanning and cholangiography. Cholangiography is the radiological study of biliary ducts after administration of a contrast medium.

Gallstone Features: The common feature of gallstone is the pain in the stomach area or in the upper right part of the belly under the ribs. Other features include nausea, vomiting, abdominal bloating and
indigestion.

Treatment for Gallstone:

• Simple Chotosterol gallstones can be dissolved over a period r-v one or two years by giving 1-1.5 gm of chemo-deoxycholic acid daily. This increases the concentration of bile adds. So, excessive concentration of bile does riot occur.
• In severe conditions, the gallbladder has to be removed (cholecystectomy). Laparoscopic surgery is a common method.