HEPATOBILIARY SYSTEM

ANATOMY

The liver is the second largest organ of the body, weighing 1200 to 1500 grams, or 4-5% of

body weight. It is located in the right upper abdominal quadrant, or the right hypochondriac and

epigastric regions, behind the lower ribs. The falciform ligament divides the liver anatomically

into two unequal lobes: right and left. Two additional smaller lobes, the quadrate and caudate

lobes are more visible in cross section. Physiologically though, the division is equal, following

the fossa for gall bladder and inferior vena cava. There is no evidence for difference in functions

among the four anatomical lobes.

The gall bladder is a saccular organ located

posterior to the liver that functions to store

bile. It has a mean capacity of 30-50 mL.

Mucosal folds, called the spiral valves of

Heister, maintain patency of the cystic duct

to allow passage of bile. Presence of fats in

the duodenum stimulate the gall bladder to

contract.

HISTOLOGY

The liver is histologically arranged into hexagonal lobules, which are primarily formed by

hepatocytes, the liver’s specialized epithelial cells that make up 80% of the liver parenchyma.

Each lobule is centered on a hepatic venule (central vein) and the hepatocytes are separated by

sinusoids into hepatic cords. Portal triads are located on the edges of the hexagonal lobules,

enclosed by connective tissues, and contain three important structures:

a. Hepatic artery that bring 25% of the total

blood into the liver

b. Portal veins that carries the other 75% of

portal blood from the lower digestive tract,

and

c. Bile ducts

Apical membranes of adjoining hepatocytes form the canalicular lumen; while the basolateral

membranes do not have direct contact. Rather, there is a space between the basolateral

membrane and the endothelial cells of the sinusoid, the space of Disse (perisinusoidal space).

Microvilli of hepatocytes extend towards the sinusoidal blood for vector transport. Thus,

hepatocytes act as a functional barrier between the canalicular lumen and the sinusoid to allow

transfer of solutes between bile and blood. Communication between hepatocytes is made

possible via tight and gap junctions and desmosomes. It is important to note that there is a

relatively small amount of connective tissues maintaining the structure of the liver; there is no

basement membrane.

There are four types of cells that make up the liver. Hepatocytes make up the bulk of the liver

parenchyma. Endothelial cells line the sinusoids and form fenestrations to control the entry of

plasma solutes and keep out red blood cells. Kupffer cells are the liver’s macrophages that lie

within the sinusoidal vascular space. Lastly, stellate or Ito cells contain large fat droplets in their

cytoplasm and form the storage of retinoids. They can transform into proliferative, fibrogenic,

and contractile myofibroblasts upon proper stimulation.

It has been noticed that the liver is functionally divided into zones. Periportal hepatocytes of

zone I reside close to the terminal portal venule and terminal hepatic arteriole. The high nutrition

and oxygen concentration microenvironment allows zone I cells to function for oxidative energy

metabolism with beta oxidation, amino acid metabolism, ureagenesis, gluconeogenesis,

cholesterol synthesis, and bile formation. They are thus the most resistant to circulatory demise

and nutritional deficiency and are the first to regenerate after a disease process. Zone III cells

are the most distal, or pericentral. Glycogen synthesis from glucose, glycolysis, liponeogenesis,

ketogenesis, xenobiotic metabolism, and glutamine formation are their primary functions.

Specialization of functions occurs because of adaptation to microenvironment. If the direction of

blood supply is reversed, zones will also be reversed.

Blood Supply To Liver

The liver receives blood from two sources: oxygenated arterial blood from the hepatic artery,

and portal blood draining from the lower GI via the portal vein. The two vessels drain into

hepatic sinusoids and then flow towards the central vein. Small central veins come together to

form three hepatic veins that return blood to the heart through the inferior vena cava.

Blood Supply To Bile Ducts

The right hepatic artery supplies the bile ducts by dividing into a rich capillary plexus that would

drain into the sinusoids. Hepatocytes then act for the bidirectional exchange of compounds

between bile and blood.

Biliary Flow

Bile is synthesized and secreted by hepatocytes into the canaliculi. Afterwhich, bile flows into

progressively larger ducts until bile reaches the duodenum via the greater duodenal papilla (of

Vater):

Terminal ductules (canals of Hering), surrounded by 3-6 ductal epithelial cells

perilobular ducts interlobular bile ducts surrounding portal vein septal ducts lobar

ducts 2 hepatic ducts common hepatic duct + cystic duct common bile duct +

pancreatic duct ampulla of Vater

LIVER CIRRHOSIS

Cirrhosis occurs as a result of progressive liver injury that involves inflammation and scarring of

the intrahepatic tissues. The liver presents histologically as a hard, shrunken and nodular tissue,

and many hepatocytes are replaced with connective tissues. As long as the normal architecture

of the liver is not lost, cirrhosis may still be reversed when the causative factors are withdrawn.

Chronic alcohol intake, viral infections, biliary stasis, and genetic defects can cause cirrhosis, or

it may also develop as a complication of other diseased organ systems like the heart.

Symptoms mainly arise from the decreased functional hepatocyte mass and the impairment of

normal blood circulation. The pattern of fibrosis can be centrilobular, pericellular, or periportal

and the zoning of hepatocytes are particularly important in the course of symptoms. Periportal

hepatocytes of zone I are most resistant to poor oxygenation and nutrition; while zone III

hepatocytes that function for glycolysis, liponeogenesis, ketogenesis, xenobiotic metabolism,

and glutamine formation are the first to be impaired by alcohol. As the disease progresses,

symptoms of impaired zone I functions, such as oxidative energy metabolism with beta

oxidation, amino acid metabolism, ureagenesis, gluconeogenesis, cholesterol synthesis, and

bile formation appear.

Pathogenesis

Fibrogenesis occurs when the fat-storing Ito cells are stimulated to produce connective tissues

and may be induced after an immune attack or during wound healing secondary to the release

of cytokines. The first occurs in HBV infection and schistosomiasis, while wound healing occurs

after Hepatitis A lesions. Fibrosis-inducing agents, like ethanol and iron, may also directly trigger

this response by increasing gene transcription of collagen or other connective tissues. Histologic

studies would initially yield a denser and non-cross-linked extracellular matrix. In the second

and irreversible stage, the liver would appear nodular and distorted with subendothelial collagen

cross-links and abundant myoepithelial cells. Alcoholic cirrhosis is typically micronodular with

<3mm in diameter. Characteristic Mallory bodies, which are cytokeratin residues, are seen in

hepatocytes.

Epidemiology

Chronic liver disease ranks as the 10th most common cause of deaths among adults in the

United States, 40% of which are due to liver cirrhosis. In the Philippines, as high as 80% of liver

cancers are preceded by cirrhosis, where liver cancer is the second leading cause of cancer-

related deaths in males.

Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis,

and it is estimated that 10 to 15 percent of alcoholics will develop cirrhosis. The severity of

alcoholic liver disease is directly related to the amount of daily alcohol intake and the duration of

alcohol abuse. Mortality rates in males are twice higher than in females due to the higher

amount of alcohol intake and because alcohol abusers are more common among males than

females. However, at any amount of alcohol, women have a higher risk of developing cirrhosis.

The underlying mechanism to this disparity is still unresolved.

Mallory BodyDense extracellular matrix

Lymphocytic infiltration

Fatty Deposits

Figure __. Normal liver

Figure __. Liver Cirrhosis. Perivenular polymorphonuclear infiltrate and ballooning degeneration of hepatocytes