The Organs of Detoxification and Elimination
As was seen in the previous chapter, many organs and tissues are involved in the absorption, the transport, the metabolism, the storage and the delimination of toxins. These highly complex processes require special properties of the organ to fulfill this function. Often, the organ itself may be endangered by disease due to the excretion, storage and movement of toxins through it.
We shall now consider these organs in more depth.
1 The Liver
The liver is one of the most important detoxifying and elimination organs in the body, and metabolically the most complex. The liver is a major organ of chemical elimination in that it takes up chemicals from blood, metabolizes chemicals, and ensures the biliary and renal secretion of toxins. The liver detoxifies a large array of external and internal toxins. It also plays a role in the cholesterol metabolism, glycolysis and gluconeogenesis, providing many of the plasma proteins necessary for carrying hormones, fats and provides clotting factors, to name a few of its numerous functions.
The principal cell in the liver responsible for the detoxifying action is the hepatocyte which facilitates the two pathways discussed in section II in dealing with mainly fat soluble toxins in order to render them hydrophilic or water soluble.
We have seen that most toxins reach the organs of elimination via the blood stream. The liver is very well perfused, and gets its blood from two sources the arterial oxygen rich blood which is delivered through the hepatic artery, and the venous blood through the portal vein from which the liver gets all the blood that is shunted from the capillaries of the gut and spleen.
Hepatocytes are practically bathed in blood as this blood transverses a system of sinusoids. This provides a very large surface for chemicals to easily diffuse into the liver cells or hepatocytes. Due to the high lipophilic character of many of the chemicals which are metabolized by the liver, to be able to enter the water soluble area, they will need carrier proteins. Several intracellular carrier proteins are present in hepatocytes.
Once inside the hepatocyte the chemical can interface with the phase I and II enzymes to undergo biotranstormation and becom water soluble. A number of these substances then diffuse back into the blood, where they will be transported to the kidneys for elimination.
2 Excretion in Bile
These bio-transformed molecules can also diffuse over the membranes of the bile canalilculus, and therefore flow into the bile duct. This is then further delivered with the other constituents to the gallbladder which excretes the bile into the intestine for fecal elimination.
In many instances we also want to facilitate the drainage of bile. The gallbladder’s primary function is to secrete bile and release it through the cystic duct. This duct joins the hepatic duct from the liver to create the common bile duct, which then empties into the upper part of the small in testion, thus into the duodenum. Bile not only carries away and neutralizes toxins, but it stimulates and aids digestions by emulsifying fats, stimulating peristalsis, and acting as a natural laxative.
3 Entero-hepatic Circulation
This is a process whereby already conjugated chemicals which are water soluble is deconjugated by hydrolytic enzymes in the gut, and then redered lipophilic again, and are once more reabsorbed by the gut. The liver is thus exposed to another round of the same toxin to reprocess it again and again, this increase the retention time for toxic chemicals in the liver, and may increase liver boxicity. Some of these metabolites are more dangerous than their original substance and as we saw above, the P450 is also a source of free radicals which will thus further damage the liver cell.
It is thus imperative to protect the liver as well during the process of Detoxification and Drainage. This will be further discussed in the section on methods of detoxification.
4 The Kidneys
The kidneys are organs specialized in the excretion of numerous water soluble toxins and metabolites, maintaining homeostasis of the organism. The kidneys detoxify
- Drugs
- Heavy metals
- Other toxins
Each kidney possesses about one million nephrons able to perform excretion. Renal excretion represents a very complex event encompassing three different mechanisms:
- Glomerular filtration by Bowman’s capsule
- Active transport in the proximal tubule
- Passive transport in the distal tubule
Blood is delivered to the kidneys via the renal artery and about 625 ml of plasma move through the kidneys per minute, and of that 125 ml is filtered through the glomelular membrane. Most of the water is then reabsorbed again in the proximal and distal tubule, so that only approximately 1-2 liters of urine is formed per day.
Some filtered substances, such as glucose will also be totally reabsorbed, so that in normal conditions there is no glucose in the urine. Other substances, many of which are harmful to the body are filtered, secreted and then minimally reabsorbed. Creatinine is such a substance, and can thus be used to test the efficiency of the kidneys in clearing harmful substances. It accumulates in the blood when the kidneys are dysfunctional. If the kidneys are damaged through disease or toxins (drugs and chemicals), their ability to excrete drugs is reduced, and in conventional medicine, the dose of drugs in needs to be adjusted accordingly.
It is important for the urine to be on the alkaline side, as it facilitates the secretion of certain drugs, like barbiturates for instance, and alkaline urine will prevent urinary tract infections.
The kidneys commonly bear the brunt of chemical toxicity since the nephron tends to concentrate the toxin and thus increase levels of toxic exposure in the tubules.
The kidneys thus also need protection and support throughout the Detoxification and Drainage stages.
5 The Matrix and Lymph
5.1 The Matrix
This forms the final biophysical layer between the cell and the regulatory organs. This system was largely forgotten since Virchow, a physician who worked in Vienna and a contemporary of Freud, saw a cell through a microscope and postulated that all diseases originated on a cellular level. Another physician working there at the time, Rokitansky, wanted to still bring in the humeral theory, but was largely ignored.
Pischinger and Heine, two modern researchers, brought this back into balance, and the newer molecular biology texts increasingly recognize the role of the matrix.
The cell on its own is actually an abstraction. The cell does not come in contact with the blood vessels, nerves, veins and lymph vessels which deliver nutrients and messengers and remove toxins. It relies for this on the biophyusical layer made up of highly polymerized sugar protein complexes called Glycoaminoglycans(GAG’s) like hyaluronic acid, chondroitin sulphate and heparin or when they are linked to a protein backbone, they are called proteoglycans(PG’s). This molecular sieve must be crossed by the entire array of metabolic products.
Sugar protein complexes are phylogenetically considered the best carriers of information. Heine and Pischinger could show that if the matrix is disturbed by a pin prick in one place, the disturbance is communicated to the whole matrix in seconds. This makes it an ideal system through which to give any information to the body. The acupuncture point is an anatomical structure originating in the matrix, a bell like structure, and it offers a wonderful ‘window’ into this system.
Unfortunately, because of the chemical and electrical charges on the GAG’s and PG’s, they also become the place where toxins are stored for a long time.
The matrix is also one of the tissues with a slow perfusion, and thus will have pattern of slow turnover. The matrix has its own biorhythm, and is dependent for instance on cortisol and thyroid hormone to be activated. During the early hours of the morning, the body goes into an ebb phase with a low cortisol, and it is during this ebb phase that the matrix will purge itself from toxic materials. Stressed patients, or patients who through a change in their sleepwake cycle have lifted or disturbed the diurnal rhythm of cortisol, will not be able to detoxify, as there may be a ‘misfiring’ between the matrix and the liver. Cortisone in high doses as medication will also disturb the innate rhythm of the body, and result in matrix toxicity. We can see that in patients who has been on cortisone therapy, as the become swollen and puffy in the matrix. Patients who are hypothyroid have been described as having ‘myxoedema’ in the older textbooks. The same swelling will be apparent in the matrix if the matrix biorhythm is disturbed. May toxins are hydrophilic and will draw fluid into the matrix. The result is edema, which we in clinical medi cine see as cyclical edema in females or as cellulite.
It is clear from the above that it the molecular sieve of the biophysical layer fails, is polluted that there will be distortion of information to and from the cell. If the disturbance is severe enough, cellular disease will ensue.
Newer molecular biological research shows that the matrix is the site for many messengers which codes for intracellular phenomena, which, if disturbed, can contribute to many disease phenomena, including cancer. (Lukashev ME, Werb Z, 1998)
5.2 The Lymph System
Apart from its role in the immune system, the lymph system alse acts as a detoxifying organ and drains most of the toxins from the matrix or connective tissues via the lymph vessels, which finally drain into the superior vena cave. The lymph system is made up of a myriad of little lymph vessels which then aggregate into larger vessels. These larger vessels are interspersed by aggregations of lymphoid tissue, which are made up of immune competent cells. These lymph nodes, as the aggregations are called, really function as super detection centers for antigens, but it is also here whereto sensitized immune cells will migrate in order to procuce millions of similar clones of that sensitized cell. The migration is called “homing” in immunology and the multiplication, cloning. The swelling we see in these lymph nodes during an infection is due to the activation of the immune cascade by these sensitized cells. This will cause an inflammation of the lymph node.
A major portion of our immune system is located in these lymph aggregations, and in fact the largest part of our immune system is found in the gut lining’s so-called Peyer’s paches. This is the reason why we can manipulate the whole of the immune system by intervening on the level of the gut lining.
Physiological considerations
The lymph system is a slow drainage system, and the propulsion of lymph towards the heart is dependent on a number of factors. Firstly, the lymph vessels have no valves, but depend on a sort of negative suction action of the truncal vessels, which is similar to that of an amphibian heart. The lymph flows relatively slowly at a rate of 1-2 ml/min, against a high resistance, whereas the venous flow is rapid at 2-3 ml/min against a low resistance. Two thirds of the body fluid is located in the intracellular space, whilst a third is located in the extra-cellular space. Of this, 75% is in the interstitial space or connective tissue and about 25% circulates as plasma. The lymph and venous flow is responsible for circulation most of the extra-cellular fluid, and the interstitial fluid in particular is drained mainly by the lymph system.
From the above it is clear that the factors which will control the fluid interchange will be:
- Oncotic pressure of the plasma and the lymph is determined by the amount of macromolecules such ass protein, and the electrolyte content such as sodium, potassium, etc, in the solution. Solutes exert a certain pressure in any fluid, as they ‘draw water’ so to speak and the more there is of them in a solution, the higher the pressure. When a patient is protein deficient for instance, through malnutrition or disease, we see that there are not enough macremolecules to keep the fluid in the vascular compartment, and the fluid will leak out into the interstitium. The result is that the oncotic pressure in the interstitium will exceed that of the plasma, and again edema will ensue.
- The hydrostatic pressure is a mechanical pressure, which can be compared to a hose pipe connected to an open tap. The smaller the diameter of the hose pipe, the higher the pressure, the more open the tap is, the higher the pressure, and if there is an obstruction like a kink in the hose, the higher the pressure before the kink, and the lower the pressure after the kink. Fluid always tends to drain from a high-pressure area to a low-pressure area over a semi permeable membrane, which is represented by the venous capillary or the lymph capillary, until the pressure is equal on both sides. Thhus if there is obstruction in the venous system, similar to a kink in the hose, there will be a high pressure in the vein, and the body will try to equalize the pressure between the vein and the interstitium, thus the fluid will also accumulate in the intrerstitium.
- If there is for instance cardiac failure we see a back pressure into the venous system, and in our hose model above, this will represent a wide open tap, with more pressure in the venous system, and then more fluid in the interstitium.
- Lastly if there is an obstruction of the lymph flow, we will see a back pressure in the lymph system and edema will again be the result. We see this in diseases of the lymph vessels like Elephantiasis, where the lymph vessel is scarred by a parasite for instance.
The lymph system as a detoxifying organ
The lymph system has a special relationship with the matrix. If is so to say as the only way out for toxins which are stored in the matrix is via the lymph system. It also means that if the matrix is overloaded with toxins as well, as the lymph system has to remove the toxic debris out of the interstitium, and at a certain point will also be clogged with these. The stimulation of lymph flow is thus one of the most important steps to achieve when cleaning the matrix.
6 The lungs
Not only does the mucosa of the respiratory tract plays an important role as a barrier to toxins as was discussed earlier, the lungs are also one of the main points of excretion of gaseous and volatile drugs such as anesthetics and even alcolol. Elimination via the lungs is typical for toxins with high volatility (e.g.organic solvents). Gases and vapours with low solubility in blood will be quickly eliminated this way, whereas toxins with high blood solubility will be eliminated by other routes.
Organic solvents absorbed by the GIT or skin are excreted partially by exhaled air in each passage of blood through the lungs, if they have a sufficient vapour pressure. The breathalyzer test used for suspected drunk drivers is based on the fact. The concentration of CO2 in exhaled air is in equilibrium with the CO2 – Hb blood content. Another example is the radioactive gas radon which appears in exhaled air due to the decay of radium accumulated in the skeleton.
A number of toxins and bacteria are also secreted in the mucous of the respiratory tract, and expectoration is thus welcomed and supported.
7 The Mucosal Membranes
Mucosal membranes form the largest part of our bodies in contact with the outside world, and they are therefore very specialized. Amucosal surface is like a micro cosmos in itself, and a good example of all the components of the auto regulatory system active in one organ. With almost 80% of the immune system forming the mucosal associated lymphoid tissue(MALT), some hormones having receptors on the mucosal cells, a full complement of nerves mediated by the autonomic nervous system, an active lymphatic drainage, and the large complement of extra-cellular matrix, the mucosal membrane comprise one of the most important regulatory organs. Not only does it form a very selective barrier with the tight junction in between the epithelial cell and adhesion molecules playing an important role in deciding what will enter the body, mucosal surfaces can also let some of the immune cells, like neutrophils through the tight junction to ingest toxic material in the lumen. It further protects against toxins by secreting chloride and other solutes tnto the lumen which will osmotically draw water in order to wash away the offender, a fact that we see as diarrhea in the gut for instance.
The integrity of these surfaces is thus of major importance in the defense against toxins.
The symbiotic gut bacteria also need mentioning here as a barrier function. Not only do they form a passive barrier against toxins coming in contact with the epithelial surface, the also contribute to the defense against toxins by producing certain metabolites which will serve as fuel for the gut lining, and as such will then help the mucosal cell to keep the integrity of the tight junction. However, due to the hydrolytic enzymes produced by them, they can also contribute to the dangerous entero-hepatic circulation mentioned above.
Absorption via gastrointestinal tract
Toxins can be ingested in the case of accidental swallowing, intake of contaminated food and drinks, or swallowing of particles cleared from the respiratory tract.
In the case of toxins biotransformed in the liver to less toxic or non-toxic metabolites, ingestion may represent a less dangerous portal of entry. After absorption in the GIT these toxins will be transported by the portal vein to the liver, and there they can be partially detoxified by biotransformation. The active area for absorption in the intestines is about 100 m2.
Some toxic metal ions use specialized transport systems for essential elements: Thalium, cobalt and manganese use the iron system, while lead appears to use the calcium system.
Many factors influence the rate of absorption of toxins in various parts of the GIT:
- Physico-chemical properties of toxins, for example, particle size is important, the smaller the size, the higher the solubility.
- Quantity of food present in the gut (diluting effect).
- Residence time in each part of the GIT (from a few minutes in the mouth to one hour in the stomach to many hours in the intestines).
- The absorption area and absorption capacity of the epithelium.
- Loca pH, which governs absorption of dissociated toxins; in the acid pH of the stomach, non-dissociated acidic compounds will be more quickly absorbed.
- Peristalsis (movement of intestines by muscles) and local blood flow.
- Gastric and intestinal secretions transform toxins into more or less soluble products; bile is an emulsifying agent producing more soluble complexes(hydrotrophy).
- Combined exposure to other toxins, which can produce synergistic or antagonistic effects in absorption processes.
- Presence of complexing/chelating agents.
- The action of micro flora of the gut comprising about 1.5 kg made up of 60 different bacterial species which can perform bio transformation of toxins.
When we thus detoxify and drain, it is also imperative to support the actions of the gut, but also to support the integrity of the barrier function in the gut.
8 The Skin
The skin forms the second largest surface of our body after the mucosa which is in constant contact with the outside world. Apart from the barrier function, it is also a major detoxifying organ, and has the same P450 system seen in the liver, as well as glutathione to take care of polycyclic aromatic hydrocarbons. The skin can absorbmany substances (like pesticides and chemicals in cosmetic products), and has to be able to detoxify them. Another important function of the skin is to protect us against the harmful UV rays from the sun. The glutathione and other free radical scavengers like catalase and super oxide dismutase are of importance, as they scavenge the free radicals formed by the UV ray exposure. Like in the liver though, induction of the detoxifying P450 pathway will also generate free radicals so that in the presence of toxins the skin is more exposed to the effects of free radicals, which leads to immunotoxicity, tissue destruction and eventually skin ageing as wekk as cabcer. Conversely, UV rays damage the detoxifying ability of the skin (the P450), and sun dam aged skin is thus less able to deal with toxins.
Due to its role in detoxification, and being one of our most important excretory organs(through sweat and evaporation), we also see the skin often bearing the brunt when other detoxifying organs like the liver are overloaded. Eczema, drug induced rashes and increased sweating are examples of this. In these cases it is thus important to support other organs like the liver for detoxification in skin disease. The liver and skin for instance break down histamine in the body through the P450. If the systems are overloaded, allergy will ensue. Histamine and other amines are also formed during the inflammatory process, and many environmental toxins, like alcoholic drinks, especially red wine can contain a large amount of histamine.
9 Sweat
Many non-electrolytes can be partially eliminated via skin by sweat, ethyl alcohol, acetone, phenols, carbon disulphide and chlorinated hydrocarbons.
10 Hair
Analysis of hair can be used as an indicator of homeostasis of some physiological substances. Also exposure to some toxins, especially heavy metals, can be evaluated by this kind of bioassay.
11 Other Routes of Elimination
Milk
Many metals, organic solvents and some organocholrine pesticides(DDT) are secreted via the mammary gland in mother’s milk. This pathway can represent a danger for nursing infants.
Saliva
Some drugs and metallic ions can be excreted through the mucosa of the mouth by saliva, for example, lead(“lead line”), mercury, arsenic, copper, as well as bromides, iodides, ethyl alcohol, alkaloids, and so on. The toxins are then swallowed, reaching the GIT, where they can be reabsorbed or eliminated by feces.
