THE LIVER

The liver, is the largest organ of the human body. This organ plays a
major role in metabolism and has a number of functions in the body, including
glycogen storage, decomposition of red blood cells, plasma protein synthesis,
hormone production, and detoxification. It lies below the diaphragm in the
thoracic region of the abdomen. It produces bile, an alkaline compound which
aids in digestion, via the emulsification of lipids. It also performs and regulates
a wide variety of high-volume biochemical reactions requiring highly specialized
tissues, including the synthesis and breakdown of small and complex molecules,
many of which are necessary for normal vital functions.

ANATOMY

An adult human liver normally weighs between 1.4–1.6 kg (3.1–3.5 lb),[4]

and is a soft, pinkish-brown, triangular organ. It is both the largest internal organ
(the skin being the largest organ overall) and the largest gland in the human
body.

It is located in the right upper quadrant of the abdominal cavity, resting

just below the diaphragm. The liver lies to the right of the stomach and overlies
the gallbladder.

Blood Flow

The liver receives a dual blood supply from the hepatic portal vein and
hepatic arteries. Supplying approximately 75% of the liver's blood supply, the
hepatic portal vein carries venous blood drained from the spleen,
gastrointestinal tract, and its associated organs. The hepatic arteries supply
arterial blood to the liver, accounting for the remainder of its blood flow. Oxygen
is provided from both sources; approximately half of the liver's oxygen demand
is met by the hepatic portal vein, and half is met by the hepatic arteries.[5]
Blood flows through the sinusoids and empties into the central vein of each
lobule. The central veins coalesce into hepatic veins, which leave the liver and
empty into the inferior vena cava.

Biliary Flow

The term biliary tree is derived from the arboreal branches of the bile
ducts. The bile produced in the liver is collected in bile canaliculi, which merge to
form bile ducts. Within the liver, these ducts are called intrahepatic (within the
liver) bile ducts, and once they exit the liver they are considered extrahepatic
(outside the liver). The intrahepatic ducts eventually drain into the right and left
hepatic ducts, which merge to form the common hepatic duct. The cystic duct
from the gallbladder joins with the common hepatic duct to form the common
bile duct.
 Bile can either drain directly into the duodenum via the common bile duct
or be temporarily stored in the gallbladder via the cystic duct. The common bile
duct and the pancreatic duct enter the second part of the duodenum together at
the ampulla of Vater.

PHYSIOLOGY

The various functions of the liver are carried out by the liver cells or
hepatocytes. Currently, there is no artificial organ or device capable of
emulating all the functions of the liver. Some functions can be emulated by liver
dialysis, an experimental treatment for liver failure.

Synthesis

Further information: Proteins produced and secreted by the liver

• A large part of amino acid synthesis

• The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the synthesis of glucose from certain amino
acids, lactate or glycerol)
o Glycogenolysis (the breakdown of glycogen into glucose)
o Glycogenesis (the formation of glycogen from glucose)(muscle
tissues can also do this)
• The liver is responsible for the mainstay of protein metabolism, synthesis
as well as degradation
• The liver also performs several roles in lipid metabolism:
o Cholesterol synthesis
o Lipogenesis, the production of triglycerides (fats).
• The liver produces coagulation factors I (fibrinogen), II (prothrombin), V,
VII, IX, X and XI, as well as protein C, protein S and antithrombin.
• In the first trimester fetus, the liver is the main site of red blood cell
production. By the 32nd week of gestation, the bone marrow has almost
completely taken over that task.
• The liver produces and excretes bile (a greenish liquid) required for
emulsifying fats. Some of the bile drains directly into the duodenum, and some is
stored in the gallbladder.
• The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide
protein hormone that plays an important role in childhood growth and continues
to have anabolic effects in adults.
• The liver is a major site of thrombopoietin production. Thrombopoietin is
a glycoprotein hormone that regulates the production of platelets by the bone
marrow.

Breakdown

• The breakdown of insulin and other hormones

• The liver breaks down hemoglobin, creating metabolites that are added
to bile as pigment (bilirubin and biliverdin).
• The liver breaks down or modifies toxic substances (e.g., methylation)
and most medicinal products in a process called drug metabolism. This
sometimes results in toxication, when the metabolite is more toxic than its
precursor. Preferably, the toxins are conjugated to avail excretion in bile or
urine.
• The liver converts ammonia to urea.

Other functions

• The liver stores a multitude of substances, including glucose (in the form
of glycogen), vitamin A (1–2 years' supply), vitamin D (1–4 months' supply),
vitamin B12, iron, and copper.
• The liver is responsible for immunological effects- the reticuloendothelial
system of the liver contains many immunologically active cells, acting as a
'sieve' for antigens carried to it via the portal system.
• The liver produces albumin, the major osmolar component of blood
serum.
• The liver synthesizes angiotensinogen, a hormone that is responsible for
raising the blood pressure when activated by renin, an enzyme that is released
when the kidney senses low blood pressure.
 THE DIGESTIVE SYSTEM
The whole digestive system is around 9 meters long. In a healthy human
adult this process can take between 24 and 72 hours.

Oral Cavity

In humans, digestion begins in the oral cavity where food is chewed. Saliva is
secreted in large amounts (1-1.5 litres/day) by three pairs of exocrine salivary
glands (parotid, submandibular, and sublingual) in the oral cavity, and is mixed with
the chewed food by the tongue.. The saliva serves to clean the oral cavity and
moisten the food, and contains digestive enzymes such as salivary amylase, which
aids in the chemical breakdown of polysaccharides such as starch into disaccharides
such as maltose. It also contains mucin, a glycoprotein which helps soften the food
into a bolus. Swallowing transports the chewed food into the esophagus, passing
through the oropharynx and hypopharynx.

Pharynx

The pharynx is the part of the neck and throat situated immediately posterior
to (behind) the mouth and nasal cavity, and cranial, or superior, to the esophagus. It
is part of the digestive system and respiratory system. Because both food and air
pass through the pharynx, a flap of connective tissue, the epiglottis closes over the
trachea when food is swallowed to prevent choking or asphyxiation. The pharynx is
also divided into 3, the oropharynx, nasopharynx, and the
hypopharynx/laryngopharynx.

Esophagus

The esophagus is a narrow muscular tube about 25 centimeters long which

starts at pharynx at the back of the mouth, passes through the thoracic diaphragm,
and ends at the cardiac orifice of the stomach. The wall of the esophagus is made
up of two layers of smooth muscles. The inner layer of muscles is arranged
circularly in a series of descending rings, while the outer layer is arranged
longitudinally. At the top of the esophagus, is a flap of tissue called the epiglottis
that closes during swallowing to prevent food from entering the trachea (windpipe).
The chewed food is pushed down the esophagus to the stomach through peristaltic
contraction of these muscles. It takes only about seven seconds for food to pass
through the esophagus and no digestion takes place.

Stomach

The stomach is a small,'J'-shaped pouch with walls made of thick, elastic

muscles, which stores and helps break down food. Stomach churning has the effect
of assisting the physical disassembly begun in the mouth. Food enters the stomach
through the cardiac orifice where it is further broken apart and thoroughly mixed
with gastric acid, pepsin and other digestive enzymes to break down proteins. The
enzymes in the stomach also have an optimum, meaning that they work at a
specific pH and temperature better than any others. The acid itself does not break
down food molecules, rather it provides an optimum pH for the reaction of the
enzyme pepsin and kills many microorganisms that are ingested with the food. It
can also denature proteins. This is the process of reducing polypeptide bonds and
disrupting salt bridges which in turn causes a loss of secondary, tertiary or
quaternary protein structure. The parietal cells of the stomach also secrete a
glycoprotein called intrinsic factor which enables the absorption of vitamin B-12.
Other small molecules such as alcohol are absorbed in the stomach, passing
through the membrane of the stomach and entering the circulatory system directly.
Food in the stomach is in semi-liquid form, which upon completion is known as
chyme.

The transverse section of the alimentary canal reveals four distinct and well
developed layers within the stomach:

• Serous membrane, a thin layer of mesothelial cells that is the outermost wall
of the stomach.
• Muscular coat, a well-developed layer of muscles used to mix ingested food,
composed of three sets running in three different alignments.
• Submucosa, composed of connective tissue that links the inner muscular
layer to the mucosa and contains the nerves, blood and lymph vessels.
• Mucosa is the extensively folded innermost layer. This is the secreting-layer
of the stomach.

Small intestine

After being processed in the stomach, food is passed to the small intestine via
the pyloric sphincter. The majority of digestion and absorption occurs here after the
milky chyme enters the duodenum. Here it is further mixed with three different
liquids:

• Bile, which emulsifies fats to allow absorption, neutralizes the chyme and is
used to excrete waste products such as bilin and bile acids.
• Pancreatic juice made by the pancreas.
• Intestinal enzymes of the alkaline mucosal membranes. The enzymes include
maltase, lactase and sucrase (all three of which process only sugars), trypsin
and chymotrypsin.
 As the pH level changes in the small intestines and gradually becomes basic,
more enzymes are activated further that chemically break down various nutrients
into smaller molecules to allow absorption into the circulatory or lymphatic systems.
Small, finger-like structures called villi, each of which is covered with even smaller
hair-like structures called microvilli improve the absorption of nutrients by
increasing the surface area of the intestine and enhancing speed at which nutrients
are absorbed. Blood containing the absorbed nutrients is carried away from the
small intestine via the hepatic portal vein and goes to the liver for filtering, removal
of toxins, and nutrient processing.

The small intestine and remainder of the digestive tract undergoes peristalsis to
transport food from the stomach to the rectum and allow food to be mixed with the
digestive juices and absorbed. The circular muscles and longitudinal muscles are
antagonistic muscles, with one contracting as the other relaxes. When the circular
muscles contract, the lumen becomes narrower and longer and the food is
squeezed and pushed forward. When the longitudinal muscles contract, the circular
muscles relax and the gut dilates to become wider and shorter to allow food to
enter.

In the small intestines, the duodenum provides critical pH balancing to activate

digestive enzymes. The liver secretes bile into the duodenum to neutralise the
acidic conditions from the stomach. Also the pancreatic duct empties into the
duodenum, adding bicarbonate to neutralize the acidic chyme, thus creating a
neutral environment. The mucosal tissue of the small intestines is alkaline, creating
a pH of about 8.5, thus enabling absorption in a mild alkaline in the environment.
[dubious – discuss]

Large intestine

After the food has been passed through the small intestine, the food enters
the large intestine. Within it, digestion is retained long enough to allow fermentation
due to the action of gut bacteria, which breaks down some of the substances which
remain after processing in the small intestine; some of the breakdown products are
absorbed. In humans, these include most complex saccharides (at most three
disaccharides are digestible in humans). In addition, in many vertebrates, the large
intestine reabsorbs fluid; in a few, with desert lifestyles, this resorption makes
continued existence possible.

In humans, the large intestine is roughly 1.5 meters long, with three parts:
the cecum at the junction with the small intestine, the colon, and the rectum. The
colon itself has four parts: the ascending colon, the transverse colon, the
descending colon, and the sigmoid colon. The large intestine absorbs water from
the bolus and stores feces until it can be egested. Food products that cannot go
through the villi, such as cellulose (dietary fiber), are mixed with other waste
products from the body and become hard and concentrated feces. The feces is
stored in the rectum for a certain period and then the stored feces is eliminated
from the body due to the contraction and relaxation through the anus. The exit of
this waste material is regulated by the anal sphincter.