Download The Detoxification System Part I: The Human Liver

The Detoxification System
Part I: The Human Liver
by
Mark J. Donohue
The liver is one of the most biochemically complex organs in the body. It is the second largest organ (the largest being
the skin) and the largest gland (synthesizes and secrets compounds) in the body. The liver serves as a gatekeeper
between the intestines and the general circulation and performs an astonishingly large number of tasks that impact all
body systems.
Anatomy and Blood Flow of the Liver
Averaging about the size of an American football in adults, the liver weighs about 3 lbs. (1.36 kg). It is reddish brown in
color and is divided into four lobes of unequal size and shape. Medical terminology related to the liver often start in
hepato- or hepatic- from the Greek word for liver (hepar).
Blood is carried to the liver via two large vessels called the portal vein and the hepatic artery. The portal vein supplies
approximately 75% of the livers blood supply and carries venous blood (returning to the heart). Three quarters of the
portal vein’s blood supply originates from the small intestines and is rich with nutrients. The remaining one quarter
originates from the spleen. The hepatic artery accounts for 25% of the blood flow to the liver and carries oxygen-rich
arterial blood from the heart via the aorta (a major vessel of the heart).
Both the portal vein and hepatic artery enter the liver dividing into smaller and smaller vessels - capillaries. These
capillaries end in the thousands of lobules of the liver. Most livers have 50,000 to 100,000 lobules. Each lobule is
composed of several different types of liver cells.
Once the blood flow reaches the liver’s lobules it continues through the sinusoids of the liver lobules. Sinusoids are small
blood vessels, similar to capillaries, and are highly permeable with fewer tight junctions and discontinuous endothelial
cells. As blood passes through the sinusoids it comes into direct contact with the liver cell’s microvilli, which are packed
with transport proteins. Here liver cells monitor and enzymatically act upon various substances within the blood.
Afterwards, the blood empties into the central vein of each lobule. The central veins coalesce into the hepatic vein,
which leaves the liver and empties into the inferior vena cava and returns to the heart.
Image: Liver blood flow
Normally, 10-15% of the total blood volume is in the liver, with roughly 60% of that in the sinusoids. When blood is lost,
the liver dynamically adjusts its blood volume and can eject enough blood to compensate for a moderate amount of
hemorrhage. Conversely, when vascular volume is acutely increased, as when fluids are rapidly infused, the hepatic
blood volume expands, providing a buffer against acute increases in systemic blood volume.
Image: Liver lobules
Cells of the Liver
There are four basic cell types that reside in the liver. These cells are the hepatocyte, the stellate cell, the liver
endothelial cell and the Kupffer cell. These so-called resident cells control many of the key functions in the liver, with
each specializing in a specific liver function.
Hepatocytes – are the main cell type in the liver and make up 70 to 80% of the liver's volume. Hepatocytes are the work
horses of the liver performing a majority of the livers daily tasks. Hepatocytes are involved in synthesizing amino acids,
protein, cholesterol, bile salts, fibrinogen, phospholipids and glycoproteins. Other functions of the hepatocytes include
the conversion and storage of carbohydrates and protein, the formation and secretion of bile and urea, and the
detoxification of toxic substances.
The hepatocyte is also the primary target of many liver diseases, including viral infections, excessive fat accumulation
and drug induced liver damage. Injury to these cells initiates the cycle of inflammation that in turn perpetuates further
liver damage.
The liver is among the few internal human organs capable of natural regeneration of lost tissue. With as little as 25%
remaining, a liver can regenerate into a whole liver again. This is predominantly due to hepatocytes acting as
unipotential stem cells (ability to renew themselves).
Hepatic Stellate Cells (HSC) or Ito Cells – reside in close proximity to the
hepatocyte and make up 5 to 8% of the liver’s volume. Under normal
conditions these cells just sit around in an inactive state, storing vitamin A
(approximately 80% of the body’s supply) and a variety of other lipids.
Under conditions of liver injury, hepatic stellate cells become activated
and act as the liver’s reserve army. When activated, these cells promote
ion movement, the production of antibodies, genesis of natural killer Tcells and the proliferation of chemical responses to stress. Researchers
believe that hepatic stellate cells play a key role in releasing collagen scar
tissue and encouraging liver scarring.
Liver Endothelial Cells (LEC) – make up 3% of the liver’s volume and form
the wall of the sinusoids, thereby separating hepatocytes from the blood flowing through the liver. Liver endothelial
cells form a single layer with gaps between each cell known as fenestra. These gaps allow for an efficient flow of
essential materials to pass from the blood to hepatocytes and play an important role in hepatic microcirculation.
In addition, these endothelial cells are rich in lysosomal enzymes which are used to digest worn out organelles, food
particles and engulf viruses and bacteria.
Kupffer cells – make up 2% of the liver’s volume and are located within the sinusoidal lining of the liver. Kupffer cells are
liver specific macrophages - a type of white blood cell (immune system) - which are phagocytic. Meaning kupffer cells
primary function is to engulf and digest and therefore, represent the main cellular system for removal of particulate
materials and microbes from the circulation. Their location just downstream from the portal vein allows Kupffer cells to
efficiently scavenge bacteria, aging red blood cells, unnecessary proteins and foreign microbes that get into portal
venous blood through breaks in the intestinal lining.
In a way, the kupffer cells are like bodyguards and assassins for the hepatocytes, protecting them from invaders and cell
refuse. However, if Kupffer cells become overburdened the filtration system will slow down. This allows a lot of bowel
microorganisms, antigens, and foreign proteins along with other waste products to enter the circulatory system as they
pass from the liver. Therefore, these cells are a significant factor in the host resistance to primary and secondary
infections. Kupffer cells facilitate and amplify the response by secreting cytokines (signaling molecules) that recruit and
expand the population of other pro-inflammatory cells in the liver.
The Biliary System
The biliary system is a series of channels and ducts within the liver that conveys bile from the liver into the duodenum
(first section of the small intestine). Bile is a complex yellowish, blue/green fluid secreted by hepatocytes. Bile consists
of water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin.
Hepatocytes secrete bile into the canaliculi - the dilated intercellular space between adjacent hepatocytes (see lobule
image above). In the canalicul, bile secretions flow parallel to the sinusoids, but in the opposite direction that blood
flows. At the ends of the canaliculi, bile flows into bile ducts, which are true ducts lined with epithelial cells. From there
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 gallbladder is a pear shaped organ that stores bile (or “gall”) between meals until needed for digestion. Typically,
bile is concentrated five-fold in the gallbladder by absorption of water and small electrolytes - virtually all of the organic
molecules are retained. During meals, especially those containing fat, the gallbladder pumps bile into the intestine. Once
in the small intestine bile’s main purpose is to emulsify dietary fats (increase surface area to help enzyme action).
Image: The Biliary System
Bile also prevents intestinal contents from decaying, enhances transit time of the stool, and is the main elimination
route for cholesterol as well as for toxins that have been broken down or detoxified by the liver.
Liver Functions
The liver serves more than 500 vital functions in the human body. These functions can be organized and grouped in a
variety of different ways. Though there is some cross over, I’ve taken the liberty of organizing the functions of the liver
into six areas:
1.
2.
3.
4.
5.
6.
Digestion
Metabolism
Synthesis
Storage
Immunological
Biotransformation
Digestive Function of the Liver
As described above one of the main functions of the liver is to assist in the digestion and absorption of fats via the biliary
system. This process begins when chyme (partially digested mass of food) from an ingested meal enters the small
intestine. Once in the small intestine acid (from stomach HCL) and partially digested fats stimulate secretion of
cholecystokinin and secretin. These hormones have important effects on both bile and pancreatic secretions.
The most potent stimulus for release of cholecystokinin is the presence of fat in the duodenum. Once released, it
stimulates contractions of the gallbladder and common bile duct, resulting in delivery of bile into the small intestine.
Secretin is secreted in response to acid in the duodenum. It simulates biliary duct cells to secrete bicarbonate and water,
which expands the volume of bile and increases its flow out into the intestine.
The secretion of bile into the small intestines functions as a detergent on particles of dietary fat which causes fat
globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is
of importance because it greatly increases the surface area of fat, making it available for digestion by lipase, a pancreatic
enzyme used to digest fats.
Bile acids are also critical for transport and absorption of the fat-soluble vitamins (A, D, E & K).
Bile is continuously secreted by the liver and stored in the gallbladder until a meal. Even though large amounts of bile
acids are secreted into the intestine every day, only a small quantity is lost from the body. This is because approximately
95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum (final section of the S.I.).
Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver.
Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic
circulation. Bile acids are then transported across the hepatocytes to be re-secreted into canaliculi. The net effect of this
enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a
single digestive phase.
Metabolic Function of the Liver
There is no organ that is more important to healthy metabolism than the liver - in many ways, it is as central to
metabolism as the heart is to the circulation of blood. Because of the crucial importance of healthy metabolism to
overall health, diseases of the liver can be devastating, leading to fatigue, malaise, and even to death.
There are three types of fuel consumed by the human cell - carbohydrate, fat, and protein - and living cells derive large
amounts of energy from the "burning" (oxidation) of these fuels.
Carbohydrate Metabolism:
It is critical for humans to maintain concentrations of glucose in blood within a narrow, normal
range. Maintenance of normal blood glucose levels over both short (hours) and long (days to
weeks) periods of time is one particularly important function of the liver.
Hepatocytes house many different metabolic pathways and employ dozens of enzymes that
are alternatively turned on or off depending on whether blood levels of glucose are rising or
falling out of the normal range. This function is vital because the primary source of energy for
the human cell, especially nerve cells, is glucose.
Glucose
Glucose itself cannot be stored therefore excess glucose entering the blood after a meal is rapidly taken up (via the
insulin independent transporter - GLUT 2) by hepatocytes and stored as the polymer (large molecule) glycogen. This
process of converting glucose to glycogen is called glycogenesis.
Later, between meals, when blood concentrations of glucose begin to decline, the liver activates other pathways which
breakdown and convert the polymer of glycogen back to glucose. The process of converting glycogen to glucose is called
glycogenolysis.
The human body can store only about 4-500 grams or about 10% of the livers weight in glycogen. This can be converted
to glucose in less than one day of normal activity, which can easily become exhausted during a fast or intense physical
activity. When this occurs hepatocytes activate additional groups of enzymes that begin synthesizing glucose out of fatty
acids and glycerol. When these molecules become depleted amino acids are used last. The ability of the liver to
synthesize this new glucose from either fatty acids or amino acids is called gluconeogenesis.
Fat Metabolism:
Because glucose is very hydrophilic (water loving), this results in co-storage of large
amounts of water. This form of energy storage takes up too much weight and volume to
be efficient. Therefore surplus glucose is metabolized into fatty acids, via a process called
lipogenesis, which are subsequently combined with glycerol to form triglycerides (fat).
Fatty acids from lipogenesis or triglycerides directly from the diet are important
metabolic fuel sources - particularly for muscle tissue. Under normal dietary
circumstances fats are used by all the body’s tissues – except the brain (CNS) – for fuel.
Fats that are not immediately oxidized and used for energy production are stored in
adipose tissue (body fat).
Triglyceride
The liver is extremely active and is the body’s primary site for oxidizing fats (either from diet or adipose tissue), to
produce energy. The liver breaks down fats for energy through a series of steps called beta-oxidation which takes place
in the mitochondria of hepatocytes.
Protein Metabolism:
The liver is the chief regulator of protein synthesis and metabolism.
The other biological fuels discussed (carbohydrates & fats) contain only the elements carbon, hydrogen and oxygen.
Proteins contain nitrogen as well and sometimes sulfur. Protein is obtained through the diet or the human body has a
metabolic pool of amino acids derived from plasma proteins (proteins in blood).
The first step in protein metabolism is the break-down of large complex molecules, via digestion of protein foods or the
catabolism of plasma protein, into simpler molecules - amino acids. The second step in protein metabolism is the
removal of the amino group (-NH2) from the molecule, referred to as deamination.
After removal of the amino group, the non-nitrogenous part of the molecule,
referred to as the “carbon skeleton” is converted to either acetyl CoA or pyruvate.
Carbon skeletons that are converted to Acetyl CoA are committed to the citric acid
/ kreb cycle, which functions solely to produce ATP – cellular energy. The carbon
skeletons that are converted to pyruvate may be used for energy production via
the citric acid / kreb cycle or they may be used to synthesize glucose
(gluconeogenesis).
The amino group (-NH2) is the nitrogen-containing part of the amino acid. Once
removed it will either be converted to ammonia - elevated levels are toxic
especially for CNS - and therefore is further converted by liver enzymes to urea for
easy excretion. Or the amino group will be used to synthesize and make a new amino acid. The further metabolism of
the amino group to ammonia or another amino acid is called transamination.
Synthesizing Function of the Liver
The liver’s hepatocytes are responsible for the synthesizing of numerous compounds such as:
Plasma Proteins:
The human body contains approximately 5 liters (5.3 quarts) of blood. Blood is a mixture of two components: 1) cells –
red blood cells, white blood cells and platelets, 2) plasma – which makes up 55% or 2.75 to 3 liters of the blood volume
and is the medium in which blood cells travel. Plasma is a clear yellowish fluid made up of 90% water which is important
for the hydration of body tissue. The remaining 10% of plasma consist of hormones, mineral ions, glucose, clotting
factors, waste products, immunoglobulins and proteins.
All plasma proteins, with the exception of gamma globulins (antibodies), are synthesized in the liver’s hepatocytes.
Some of the more common plasma proteins and their functions are:

Albumin – accounts for 60% of total plasma protein and is
essential for maintaining osmotic pressure needed for proper
distribution of body fluids to all body tissues. It also acts as a
plasma carrier or transporter of various substances (hormones,
lipids, vitamins, minerals, etc.).

Globulins – make up 35% of total plasma protein. There are
four types of globulins alpha1, alpha 2 and beta which and are
also involved in the transporting of various substances. The
fourth type - gamma are involved in immune processes, but are
not synthesized by the liver rather by lymphocytes (plasma
cells).

Fibrinogen or Factor I – makes up 4% of total plasma protein
and is a sticky, fibrous coagulant essential in the formation of blood clots. This is done by thrombin (another
plasma protein) reacting with fibrinogen to create fibrin a stringy substance which creates a clot.
Hormones:
A hormone is a chemical compound that is produced and secreted in one part of the body that effect cells in other parts
of the body. Essentially, hormones are chemical messengers that transport a signal from one cell to another via the
blood stream. The liver synthesizes and secretes several important hormones.

Angiotensinogen – technically a pro-hormone (precursor to a hormone). Angiotensinogen plays an important
role in the rennin-angiotensin system whose primary function is to regulate blood pressure and water balance.

Estrogen – though the hormone estrogen is found at significantly higher levels in females (being produced
primarily in the ovaries), estrogen is also found in males. This is because estrogen is also synthesized, in smaller
amounts, in the liver and adrenal gland of both men and women. In both sexes estrogen is responsible for
regulating certain functions in the reproductive system (e.g. menstrual cycle, sperm maturation).

Hepcidin – is the master regulator of iron homeostasis in the body. Hepcidin does this by preventing the
absorption of iron from the digestive tract and by also inhibiting the release of stored iron from macrophages
and hepatocytes.
This function not only helps to maintain homeostatic levels of iron in the body fluids but also serves as a defense
against pathogenic bacteria. Many pathogens require substantial amounts of iron for their virulence and the
release of hepcidin in response to infection starves them of this needed iron.

Tri-iodothyronine (T3) – is a metabolically active thyroid hormone that is produced from thyroxine (T4) - a prohormone produced by the thyroid gland. The conversion of T4 to T3 takes place in the thyroid, brain, liver and
various other body tissues. Thyroid hormones act as the body’s thermostat, regulating the rate at which virtually
all biochemical reactions occur in the body - metabolism.

Thrombopoietin (TPO) – a hormone produced primarily in the liver, whose function is to regulate platelet
production which is essential for blood clotting.

Insulin-like growth factor 1 (IGF-1) - is a hormone synthesized in
the liver which is similar in molecular structure to insulin. Growth
hormone released from the pituitary gland binds to receptors on
the surface of hepatocytes which stimulates the synthesis and
release of IGF-1. IGF-1 then stimulates systemic body growth. The
levels of IGF-1 in the blood are highest during the years of puberty
which is a time of rapid growth.
Nutrients:
In the liver some nutrients are directly synthesized while others are converted into their more biologically active forms.

B Vitamins – a compound is called a vitamin when it cannot be synthesized in sufficient quantities by the body
and must be obtained from the diet. Therefore, the liver does not directly synthesize B-vitamins. Rather the liver
converts some B vitamins from the diet, which are in a form that cannot be used by the body, into their
biologically active co-enzyme forms. For example the liver converts:
Dietary B Vitamin
Thiamin B1
Riboflavin B2
Pyridoxal B6
Folate B9
Coenzyme Form
Thiamin pyrophosphate (TPP)
Flavine mononucleotide (FMN)
Flavine adenine dinucleotide (FAD)
Pyridoxal phosphate (PLP)
Tetrahydrofolate (THFA)

Iron and Copper – in order for iron and copper to be bio-available they must be bound to their appropriate
bloodstream transport or storage proteins. The synthesis of these proteins, such as transferring, ferritin and
ceruloplasmin and the binding of the minerals takes place in the liver.

Carnitine – the liver synthesizes carnitine from the amino acid lysine and methionine. Carnitine escorts fats into
the mitochondria, where the fats may be burned to generate ATP – bio-energy.
NOTE – virtually every nutrient, whether it is a vitamin, mineral or amino acid, must be converted by the liver into its
proper biochemical form in which the nutrient may be stored, transported or used in cellular metabolism. If the liver
fails to do this, then even the most well absorbed, high potency, broad spectrum supplements will be useless at best and
possibly even mildly toxic.
The forms in which nutrients are found in supplements and foods are NOT the final, active biochemical forms used by
the cells. And even if you do get the active coenzyme form of a nutrient from a food or supplement, it will usually be
broken down during digestion. So there's no getting around the critical role of the liver in bio-activating the nutrients we
get from foods or supplements.
Cholesterol & Lipoproteins:
Cholesterol is an essential structural component of cell
membranes, where it is required to establish proper
membrane permeability and fluidity. Within the cell
membrane cholesterol also functions in intracellular
transport, cell signaling and nerve conduction.
In addition, cholesterol is an important component for the
manufacture of bile acids, steroid hormones (estrogen,
progesterone, testosterone, cortisol, aldosterone), and
several fat-soluble vitamins (vit.D).
Cholesterol is either obtained from the diet - cheese, egg
yolk, beef, pork, poultry and shrimp - or synthesized in a
variety of tissues – adrenal cortex, skin, intestine, testes and
liver. About 10 - 20% of total daily cholesterol production
occurs in the liver.
The liver is the main organ responsible for the regulation of
cholesterol levels circulating throughout the bloodstream.
The liver does this by:
Image: Cell membrane

Synthesizing cholesterol

Varying the amount of cholesterol it synthesizes based on the amount of cholesterol intake from dietary sources
(negative feedback loop).

Synthesizes the various lipoproteins involved in transporting cholesterol and lipids throughout the body.
Lipoproteins are a biochemical assembly that contains both lipids (fat) and protein, for example – high density
lipoprotein (HDL) and low density lipoprotein (LDL).

Removes cholesterol from the body by converting it to bile salts and excreting it in the bile.
Storage Function of the Liver
The liver acts as a storage facility for certain vitamins, minerals and sugars such as:
Glycogen
Lipids
Cholesterol
Vitamin
Vitamin
Vitamin
Vitamin
Folate
A
D
K
B12
Iron
Copper
Zinc
Immunological Function of the Liver
The liver is an immunologically distinct organ, though as such the liver receives little attention, despite the fact that it
fulfills a number of roles in the defense of the body. Case in point; the reticuloendothelial system, which most people
have never heard of, is an integral part of the body’s defenses – the immune system.
The reticuloendothelial system consists of a special class of cells widely distributed in the body. The function of these
cells is to engulf, digest and destroy bacteria, viruses, foreign substances and worn out or abnormal cells. This special
class of cells are called macrophages (immune cells). Eighty percent of the body’s resident macrophages are found in
the liver and once inside the liver are referred to as Kupffer cells.
Picture: Macrophage engulfing foreign particle
Described earlier, Kupffer cells are essential to the liver’s primary function, which is cleansing the blood of foreign
materials and toxic substances. When no foreign materials are present, Kupffer cells are in a resting state. Kupffer cells
can be activated by numerous molecules, for example: bacterial endotoxins. An endotoxin is a toxin that forms part of
the cell wall of certain bacteria and is only released upon destruction of the bacterial cell.
As endotoxins cross the intestinal barrier and enters the bloodstream, it interacts with the Kupffer cells in the liver,
thereby activating them. When activated, Kupffer cells secrete a variety of cytokines, including a molecule called tumor
necrosis factor alpha (TNF–α) and several types of interleukins. All of these molecules can act as inflammatory
cytokines—that is, they induce an inflammatory response necessary to remove the offending toxic or foreign molecules
and initiate the healing process.
In addition to producing cytokines, activated Kupffer cells are the major source of reactive oxygen species (ROS) in the
liver. Reactive oxygen species, also known as free radicals, are oxygen containing molecules that are highly reactive with
other complex molecules in the cell (e.g., proteins, fat molecules and DNA). Reactive oxygen species such as superoxide,
hydrogen peroxide, and hydroxyl radicals have been implicated in the development of liver damage. Excessive levels of
reactive oxygen species within a cell and/or the lack of molecules that can eliminate them (i.e., antioxidants) leads to a
state called oxidative stress that is detrimental to the cell.
The liver is also a major contributor to the formation of lymph. Lymph is a
clear, watery fluid that resembles the plasma of blood. Lymph flows through an
elaborate network of channels and ducts called lymph vessels. Lymph, lymph
vessels and lymph organs such as - lymph nodes, thymus, spleen and bone
marrow- are collectively referred to as the lymphatic system. The lymphatic
system has several functions, but one of the primary functions is to fight
infections and defend the body against diseases. It does this by producing
special white blood cells called lymphocytes that produce antibodies.
Lymph is the medium in which lymphocytes, along with macrophages, travel
through the lymphatic system where they come in contact with foreign
particles and germs - hopefully destroying them. The function of the lymphatic
system is considered by many to really be part of the immune system.
It is estimated that 25 to 50% of lymph flowing through the major lymphatic vessel – the thoracic duct - is produced by
the liver. This occurs due to the large pores or fenestrations in the liver’s sinusoidal endothelial cells. These openings
allow fluid and proteins in the blood to flow freely into the space between the endothelium and hepatocytes – “the
space of Disse" - forming lymph. Lymph flows through the space of Disse to collect in small lymphatic capillaries
associated with portal triads.
Another important immunological function of the liver is the production and secretion of a specific immunoglobulin.
Immunoglobulins, also known as antibodies, are gamma globulin proteins that are found in blood and other bodily fluids
and are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.
Immunoglobulins come in different varieties known as isotypes of which there are five known types in the human body
– IgA, IgD, IgE, IgG and IgM. “Ig” stands for immunoglobulin and each one differs in their biological properties, functional
locations and ability to deal with different antigens (foreign particle).
The immunoglobulin we are concerned with is IgA, which is found
in mucosal areas – intestine, respiratory tract, urogenital tract,
prostate, saliva, tears, and breast milk - and prevents colonization
by pathogens (germs). A selective lack of immunoglobulin A,
which constitutes the most common type of immunoglobulin
deficiency, appears in about 1 in 400 individuals. Common
symptoms are recurring infections of mucosal surfaces – nose,
throat, lungs, intestines as well as diseases of the mucosal surfaces
- respiratory allergies, gastrointestinal diseases, autoimmune
diseases, and malignant tumors.
The liver plays a major role in secretion and / or clearance of circulating IgA into the upper gastrointestinal tract. IgA in
the sinusoidal blood combines with secretory components (SC) on the surface of hepatocytes before being transported
into the bile. It has also been found that IgA containing plasma cells are numerous in human biliary mucosa where they
release IgA into the bile ducts. Together the proportion of IgA in human bile that is derived from local synthesis within
hepato-biliary tissues is high – about 50%.
Biotransformation Function of the Liver
The main function of the small intestine is to absorb and it is not picky about what it absorbs. Consequently, it absorbs
many substances that are potentially noxious (harmful) or at least of questionable value. Therefore, it is up to the liver
to get rid of them. This is not an easy task, especially for lipophilic molecules (affinity for lipids /fats), as everything that
leaves the body (via body fluids and waste) is more or less hydrophilic (watery).
The liver’s solution is a process called biotransformation, which is covered in more detail in part II of this report.
References
Human Physiology, by Wikibooks contributors, 2007
Nagura H. Phillip D.S., Nakane P.K., Brown W.R., IgA in Human Bile and Liver, The Journal of Immunology, 126(2): 587-594 (1981)
Nagura H. Tsutsumi Y. Hasegawa K. Watanabe P.K., IgA plasma cells in biliary mucosa: a likely source of locally synthesized IgA in
human hepatic bile, Clinical Experimental Immunology, 54: 671-680 (1983)
Ohtani O. Ohtani Y., Lymph Circulation in the Liver, The Anatomical Record, 291: 643-652 (2008)
Wheeler M.D., Endotoxin and Kupffer Cell Activation in Alcoholic Liver Disease, National Institute of Health, (2004)
World Wide Web:
 Brown University
 Colorado State University
 General Biology by Jim Kimball PhD, 2009
 Lecture – Arno Helmberg, Innsbruck Medical University, Austria
 National Anemia Action Council
 On-Line Biology Book by Michael Farabee 2006
 University of South Australia
 Wikipedia