Organs Of Protection And Detoxification
Toxins can enter the body in three ways: by absorption through the skin; by inhalation through the respiratory tract into the lungs; or by ingestion through the
mouth into the gastrointestinal tract. The skin, lungs, intestines, and kidneys have all developed some protective mechanisms and
methods of detoxification, although the liver is the body's major organ of detoxification.
The liver
The liver is a dome-shaped gland that fits under the diaphragm, just under the right ribcage. It is considered a gland because it
secretes bile, and it is the largest gland in the body.
The liver is divided into two major regions, the right and left lobes. The right lobe, which has three smaller lobes, is larger than
the left, which has two smaller lobes. Each of the five lobes is composed of compartments called liver lobules.
The central vein passes through the center of each lobule and drains away waste products from the liver. The cells of the lobule closest to the central vein are known as
centrilobular hepatocytes (liver cells). Cytochrome P-450 is most highly concentrated in these cells, and detoxification activity is also highest in this area.
On the other side of the liver, the hepatic artery and portal vein are known as the periportal system. The hepatic artery supplies
oxygen to the liver directly from the heart and lungs. The cells of the lobule closest to the hepatic artery have the highest concentration of oxygen in the liver. They also have
the highest concentration of nutrients because the liver is the first organ to receive nutrients absorbed by the GI tract, delivered by
the portal vein. These cells also have the highest exposure to xenobiotics in the liver, as well as higher concentrations of glutathione and transaminase enzymes. The levels of these enzymes are tested in the standard blood chemistry test for liver function.
- HOW TOXINS ENTER THE LIVER
- The liver is situated to receive a majority of the venous blood from the lower body, the kidneys, the spleen, and the gastrointestinal
tract. Approximately 1500 ml of blood, containing many different toxins, flows through the liver every minute.
The liver is the main organ for biotransformation of chemicals. However, it is susceptible to tissue injury from the toxic effects
of chemicals, and if it becomes overloaded, can be permanently damaged. Some chemicals are toxic to specific parts of the liver.
- PROTECTIVE DEVICES
- Adequate levels of the conjugation enzymes needed for Phase II are protective for the liver. They help prevent the buildup of toxic
substances formed as a result of biotransformation during Phase I of detoxification. The presence of adequate antioxidants to quench
free radicals is also protective for the liver.
Even when 80 percent of the cells of the liver are damaged, the liver can continue to
function, but with reduced efficiency. It has the ability to restore and replace these damaged cells, and can recover if the sources of the toxins are removed.
- DETOXIFICATION
- The bulk of toxic substances are detoxified in the liver. The liver removes chemicals that have been absorbed into the blood, and excretes them into the bile stored in the gallbladder. Both Phase I and Phase II detoxification processes are active in the cells of the
liver, and the liver's cytochrome P-450 system is the body's first-line site for the detoxification of foreign chemicals.
Over 300 known chemicals can induce (increase) enzyme system activity in the liver. These chemicals can lead to more enzymes being present and a faster rate of detoxification. They also increase the amount
of endoplasmic reticulum (membranes in the cell where detoxification occurs) in the liver.
While some chemicals increase the liver's metabolic action, others inhibit the activity of cytochrome P-450 and other detoxification enzymes. Chemicals can cause
inhibition in several ways:
- competition between two or more compounds for the same detoxifying enzymes
- inhibition of enzyme synthesis
- inactivation or destruction of enzymes or the endoplasmic reticulum
- overwhelming of the detoxification enzyme systems
- depletion of necessary cofactors for Phase II
Inhibition of cytochrome P-450 can lead to the buildup of toxins in the body. For example, theophylline is a drug used to control
asthma and belongs to the same family as caffeine. It can build up to toxic levels if the patient is given erythromycin simultaneously, which inhibits the cytochrome P-450
enzyme system from breaking down the theophylline. Erythromycin and antifungals such as ketoconazole can also inhibit the breakdown of Seldane, an antihistamine.
Because the resulting high levels of Seldane can cause heart rhythm disturbances, it has been taken off the market.
The kidneys
The principal excretory organs in all vertebrates, the kidneys lie in the back of the abdominal wall, one on each side of the backbone. They are bean-shaped, and on the
concave side of each one is an area called the hilus, where the renal (kidney) artery enters and the renal vein exits. The adrenal glands
sit on top of the kidneys. The kidneys are also regulatory organs, helping to maintain homeostasis (physiological balance between all body organs).
Each of the kidneys consists of the outer cortex and the inner medulla. The cortex receives 85 percent of the total renal blood flow
and is composed of nephrons, which are excretory units. Each kidney has over one million nephrons. Each nephron has three parts:
- the vascular or blood circulation component, composed of interconnected capillaries;
- the glomerulus, the filtering tissues of the kidney; and
- the tubules, small tubes or ducts that reabsorb 98 to 99 percent of the salts and water filtered by the glomerulus, for the body's use. The last tubule, the collecting duct, concentrates the remainder of the fluid as urine.
The nephron's tubular element joins the ureter, which exits from the same side of the kidney as the renal vein and artery. The ureter carries the urine to the bladder, a
balloon-shaped storage chamber. As urine enters the bladder, its walls of smooth muscle unfold to the volume needed to contain the urine. When the bladder becomes distended, receptors are stimulated to contract
the bladder. The urine then flows under voluntary control through the urethra, and out of the body.
Kidneys filter out cellular waste, metabolic waste (mostly breakdown products of protein metabolism), drugs, and toxins from the blood. In addition to filtering the blood
and draining wastes, the kidneys eliminate foreign chemicals from the body, and regulate the body's pH balance, calcium metabolism, electrolyte balance, fluid balance, and
extra cellular volume (circulating fluid outside the cells). The kidneys produce a hormone that stimulates red blood cell production, helps to regulate blood pressure, and
also plays a role in vitamin D metabolism.
- HOW TOXINS ENTER THE KIDNEYS
- The kidneys have an even higher blood flow than the brain, liver, or heart, and receive 25 percent of the body's total blood volume,
causing high exposure to chemicals carried in the blood. They reabsorb and redistribute about 99 percent of the blood volume received, and 0.1 percent of the blood filtered becomes urine.
- PROTECTIVE DEVICES
- An adequate supply of Phase II enzymes is protective for the kidney, as is the intake of adequate fluids. Kidney stones, which can
damage the kidneys, can form when there is too little fluid. Accurate pH control of the urine is also protective, as kidney stones
tend to form when urine pH is not optimum.
Kidney disease can be quite advanced before it is detected, as the kidneys can lose 80 percent of their function before symptoms appear.
- DETOXIFICATION
- The kidneys excrete chemicals that have been prepared by Phase II detoxification in other parts of the body. Phase II converts
lipid-soluble nonpolar substances into more polar substances. This makes them less fat-soluble and less likely to be reabsorbed by
the kidney tubules. They are then available for excretion in the urine.
Some chemicals (for example, ammonia) are secreted by the tubules and move into fluid in the lumen (interior) of the tubule, where they are then eliminated from
the body in the urine. Tubule cells are also capable of catabolizing (breaking down) certain organic compounds, which destroys them even though they are not excreted in the urine.
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