Monday, August 9, 2010


Excretory/Urinary System
As animals perform their various metabolic processes, protein and nucleic acid, both of which contain nitrogen, are broken down. While some of the nitrogen is used to manufacture new nitrogen-containing molecules, much of it cannot be used for this purpose and must be disposed of as waste. Typically, the first nitrogen-containing molecule that forms is ammonia (NH3, which is very water-soluble, forming NH4OH, a strong base. In some way, this ammonia must be gotten rid of before it raises the pH of the body fluids. Because ammonia is so water-soluble, aquatic animals often can get rid of it just by diffusion into the surrounding water. That’s one reason why the water in your aquarium gets “bad” and needs to be changed, and why not changing the water could kill the fish. However, ammonia doesn’t readily go from body fluids into air, so terrestrial animals need other ways of getting rid of nitrogenous wastes.
The two most common substances used by terrestrial animals to get rid of excess nitrogen are urea and uric acid. Many animal species that aren’t terribly concerned about water-loss, including humans, convert the ammonia to urea, which is water-soluble and excreted in a water-based solution. Other organisms such as birds, insects, or lizards, especially if they live in an arid area, must conserve water whenever possible, thus convert the NH3 to uric acid. Uric acid is not water-soluble, thus can be excreted with little, if any, water with it. This is the white goo in bird droppings. While the major portion of human nitrogenous waste is in the form of urea, humans typically excrete some uric acid, too. Uric acid is another kind of purine like the adenine and guanine in our DNA (structure to the right).
Gout is a disorder in which humans start to accumulate more than the usual amount of uric acid (caused by either the body manufacturing excess uric acid or the kidneys not excreting enough of it) and since it’s not water-soluble, it gets stored in the body, frequently in toe joints, causing pain and deformation of the joints involved as well as the formation of kidney stones. Traditionally, people who had gout were put on diets low in purines to try to help alleviate the condition, but according to the Merck Manual, now these people are doped up with drugs rather than given nutritional counseling: [“Drugs are so effective in lowering the serum urate concentration that rigid restrictions of the purine content of the diet usually is unnecessary.”]. Typically, gout is treated with colchicine, a deadly poison (see further notes below)! Caffeine and its relatives, theobromine (in cocoa), and theophylline (in tea) are classified as xanthines (a subgroup within the purines), thus it would make sense that people with gout should be counseled to avoid coffee, tea, and chocolate.
Some insects, notably blowfly larvae (larvae of those shiny green or blue flies) excrete their nitrogenous wastes as allantoin, another purine. Allantoin is known to be a “cell-proliferant,” thus is used to help wounds to heal. For hundreds of years, people have recognized that the presence of blowfly larvae in a gangrenous wound actually helped it to heal better. From about the turn of the century until the invention of a lot of synthetic drugs, blowfly larvae were raised aseptically, and used to treat severe wounds. With the increase in availability of chemicals after World War II, the use of blowfly larvae declined, but I’ve heard of several cases lately where, for some reason, this treatment was necessary and/or preferred over synthetic drugs. It has been found that the fly larvae only eat dead, gangrenous tissue, leaving the live, healthy tissue, and since their nitrogenous waste is allantoin, that stimulates the wound to heal, usually with less scaring. In this procedure, small, sterile larvae are introduced into the wound and, if needed, traded for other small ones when they get big.
We excrete nitrogenous wastes via our kidneys. Our kidneys are located on either side of the spine, just up under the bottom ribs. They are well supplied with blood via the renal artery and renal vein. Urine made in the kidney collects in the renal pelvis within the kidney, then flows down the ureter to the bladder where it is stored until voided. From the bladder, the urine flows to the outside via the urethra, (which in the male also serves as part of the reproductory tract).

The kidney is composed of an outer layer, the cortex, and an inner core, the medulla. The kidney consists of repeating units (tubules) called nephrons. The “tops” of the nephrons make up or are in the cortex, while their long tubule portions make up the medulla. To the right is a diagram of an individual nephron. Each nephron has a closely associated blood supply. Blood comes in at the glomerulus and transfers water and solutes to the nephron at Bowman’s capsule. In the proximal tubule, water and some “good” molecules are absorbed back into the body, while a few other, unwanted molecules/ions are added to the urine. Then, the filtrate goes down the loop of Henle (in the medulla) where more water is removed (back into the bloodstream) on the way “down”, but the “up” side is impervious to water. Some NaCl (salt) is removed from the filtrate at this point to adjust the amount in the fluid which surrounds the tubule. Capillaries wind around and exchange materials with the tubule. In the distal tubule, more water and some “good” solutes are removed from the urine, while some more unwanted molecules are put in. From there, the urine flows down a collecting duct which gathers urine from several nephrons. As the collecting duct goes back through the medulla, more water is removed from the urine. The collecting ducts eventually end up at the renal pelvis which collects the urine from all of them. The area where the collecting ducts enter the renal pelvis is a common area for formation of kidney stones, often giving them a “staghorn” shape.
(clipart edited from Corel Presentations 8)
Antidiuretic hormone (ADH) from the pituitary is one factor influencing urine production. ADH promotes water retention by the kidneys, and its secretion is regulated by a negative feedback loop involving blood water and salt balances. ADH helps the kidney tubules reabsorb water to concentrate the urine. When the blood water level is too high (when you’ve been drinking a lot of liquids), this acts as a negative feedback to inhibit the secretion of ADH so more water is released. Ethanol also inhibits secretion of ADH, so a person who consumes a lot of alcoholic beverages could excrete too much water (and maybe even become dehydrated). Many diuretics work by interfering with ADH production, thus increasing the volume of urine produced. These diuretic effects are one reason why a person drinking beer (alcohol) or coffee (caffeine) needs to urinate more frequently.
When a person’s kidneys cease functioning, due to illness or other causes, renal dialysis can be used on a short-term basis to filter the person’s blood. This is not a perfect process; it can’t do everything a person’s kidneys can. Typically a person is put on renal dialysis as a temporary measure to extend the person’s life until a kidney transplant can be found. While life-saving, this procedure is often very inconvenient and stressful for the person. It requires spending long periods of time, several days a week, hooked up to the dialysis machine: the person’s blood must actually pass into the dialysis machine so the wastes can be filtered out, and then the blood is returned to the person’s body. This, combined with symptoms caused by the renal failure (the inability of the person’s kidneys to function) often preclude working at a job to earn the money to pay for the treatment. People can get by with one kidney, and the closest tissue match for a kidney transplant is often a sibling. However, as one former student who was a kidney-transplant recipient pointed out, even kidney transplants don’t last “forever”. Besides the constant workings of the person’s immune system to reject this foreign tissue, whatever disease caused the problem in the first place will probably eventually also affect the transplanted kidney. Since the same donor can’t provide another new kidney, this may mean going back on dialysis and hoping a matching donor (accident victim) can be found before it’s too late.
Some diseases and disorders of the excretory system include:
• Nephritis is an inflammation of the glomeruli, due to a number of possible causes, including things like strep throat. Symptoms include bloody urine, scant urine output, and edema (swelling/puffliness). Another, more severe form, is due to an autoimmune attack on the glomeruli. Other types of nephritis affect the tubules.
• Nephrosis also affects the glomeruli, and is characterized by excretion of abnormally large amounts of protein (often causing “foamy” urine) and generalized edema (water retension/swelling) throughout the whole body, especially noted as “puffy” eyelids. Because these people’s kidneys often do not handle sodium properly, a low-salt diet is usually prescribed. My younger brother developed nephrosis at age 4, and to control it, had to stay on a no-added-salt diet and take prednisone on a regular basis from then until age 16, at which point, his body finally responded positively to being weaned off the drug.
• Most urinary tract infections (UTIs) are caused by Gram negative bacteria such as E. coli. If there is an obstruction of the urethra, catheterization may be needed, but as a general rule, catheterization in cases of UTI is contraindicated because it can actually introduce pathogens and make the infection worse. Women tend to acquire more urethral and bladder infections than men, perhaps because the opening of the urethra is closer to the anus. The way a woman cleans the area after relieving herself can influence her chances of contracting a UTI and/or vaginal infection. When parents are toilet-training toddlers, the common mistake is to wipe young girls from back to front. The toddlers get used to this feeling, and when they start to wipe themselves, they also go from back to front. This technique wipes bacteria from the anal area towards or into the ends of the vagina and urethra. Rather, young girls should be trained to wipe from front to back, and women who were not trained this way should make a conscious effort to change their habits.
• There are a variety of types of kidney stones depending on what conditions caused their formation. According to the Merck Manual, in the United States, about 80% are calcium oxalate (and/or other calcium-based stones), 5% are uric acid, 2% are cystine, and the other 13% due to magnesium ammonium phosphate or other causes. Stones may be microscopic to large “staghorn” stones that fill the whole renal pelvis. Often, as the stone is passed down the ureter, the person experiences much pain, and the affected kidney may even temporarily become nonfunctional. Stones may be broken up by ultrasound so they can be passed more easily, but large stones may have to be surgically removed. If possible, the underlying cause of the stone(s) should be identified and alleviated. For example, calcium stones might be caused by anything from a parathyroid gland problem to too much vitamin D to some forms of cancer to a genetic predisposition.
More information on colchicine
If you had gout, would you rather, as something to try first, modify your diet or take this substance?
• From a chemical dictionary: Colchicine is an alkaloid extracted from Colchicum autumnale, the autumn crocus. It is used in medicine and to induce chromsome doubling in plants. It is very poisonous.
• From an organic chemistry text: “Colchicine has the interesting property of arresting cell mitosis at the stage just after division of the chromosomes. It dissolves the spindles connecting the chromosomes, resulting in a cell with double the original number of chromosomes.” It is used to produce polyploid plants.
• From a cell physiology book: “Colchicine causes the chromosomes to contract to the metaphase condition in which sister chromatids are spread and are more readily observed than in controls, but it prevents anaphase,” and “Colchicine apparently inhibits cell division by disorganizing the mitotic spindle, without stopping growth or duplication of various organelles in the cell. Chromosomes duplicate themselves, but the spindle fibers that form are disoriented, resulting in polyploidy which, in some species, persists even after the poison is removed” (which means that whatever cells manage to survive the treatment will have more than usual chromosomes).
• From a cytology book: In cytology, colchicine is commonly used to arrest cells in metaphase of mitosis because that’s when it’s easiest to get a chromosome count. Colchicine disrupts the spindle apparatus. Colchicine treatment results in retention of most of the cells in metaphase, and if cells are treated for an extended time, divisions of the chromosomes continue without divisions of the cell, so polyploids develop. The fundamental action of colchicine seems to be the prevention of the proper assembly of protein molecules into the microtubules of the cytoskeleton and mitotic spindle. “Gout symptoms result from the phagocytic action of leucocytes on urate crystals deposited in the joints. Colchicine may relieve this condition by interfering with the microtubules on which phagocytic activity depends” (Which means that the WBCs that normally engulf and kill foreign invaders cannot do so because their internal cytoskeleton is all messed up: this would mean that the person’s immune system and ability to fight off infections would also be reduced. However, the uric acid crystals are still there, and have not been dealt with.). Colchicine binds to the protein subunits (that make up microtubules) inhibiting their assembly into the microtubules.
• From the Merck Manual: Colchicine is also used to treat famial Mediterranean fever. It is thought that “possibly it prevents normal cellular response to inflammation” (which means that they think that it supresses proper immune function (phagocytosis).
• From an old PDR: Colchicine can produce a temporary leucopenia, a decrease in the number of WBCs, that is followed by leucocytosis, an increase in the number of WBCs. Colchicine alters neuromuscular function, intensifies gastrointensinal activity by neurogenic stimulation (thus can cause problems, especially if someone also has an ulcer), causes a number of other NS symptoms, depresses the respiratory center, constricts the blood vessels, causes hypertension, and lowers body temperature, to list a few of its effects. The reference cautions against its use during pregnancy because of its effect of stopping mitosis. In some animals it has been found to be teratogenic (it causes birth defects) and the possibility of such effects in humans has been reported! Colchicine has been reported to adversely affect spermatogenesis in animals. “Since colchicine is an established mutagen, its ability to act as an carcinogen must be suspected.” Colchicine may cause loss of hair (which makes sense if it’s inhibiting the cell division needed for hair to grow).
Concurrently administered drugs that promote urate (uric acid) excretion by the kidneys can actually cause the formation of uric acid kidney stones, especially if the urine is acidic.
• From an herb book entry on Colchicum autumnale: “Most of the ancient and medieval writers [herbalists], except the Arabic physicians, considered Colchicum too poisonous to use. . .” Its use for gout can be traced to research done in the 1700s.
Every one of us depends on the process of urination for the removal of certain waste products in the body. The production of urine is vital to the health of the body. Most of us have probably never thought of urine as valuable, but we could not survive if we did not produce it and eliminate it. Urine is composed of water, certain electrolytes, and various waste products that are filtered out of the blood system. Remember, as the blood flows through the body, wastes resulting from the metabolism of foodstuffs in the body cells are deposited into the bloodstream, and this waste must be disposed of in some way. A major part of this "cleaning" of the blood takes place in the kidneys and, in particular, in the nephrons, where the blood is filtered to produce the urine. Both kidneys in the body carry out this essential blood cleansing function. Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration. This is called the filtration fraction. The rest of the blood (about 80%) does not go through the filtering portion of the kidney, but flows through the rest of the body to service the various nutritional, respiratory, and other needs that are always present.
For the production of urine, the kidneys do not simply pick waste products out of the bloodstream and send them along for final disposal. The kidneys' 2 million or more nephrons (about a million in each kidney) form urine by three precisely regulated processes: filtration, reabsorption, and secretion.
Figure 3. Urine formation takes place in the nephron.

Urine formation begins with the process of filtration, which goes on continually in the renal corpuscles (Figure 3). As blood courses through the glomeruli, much of its fluid, containing both useful chemicals and dissolved waste materials, soaks out of the blood through the membranes (by osmosis and diffusion) where it is filtered and then flows into the Bowman's capsule. This process is called glomerular filtration. The water, waste products, salt, glucose, and other chemicals that have been filtered out of the blood are known collectively as glomerular filtrate. The glomerular filtrate consists primarily of water, excess salts (primarily Na+ and K+), glucose, and a waste product of the body called urea. Urea is formed in the body to eliminate the very toxic ammonia products that are formed in the liver from amino acids. Since humans cannot excrete ammonia, it is converted to the less dangerous urea and then filtered out of the blood. Urea is the most abundant of the waste products that must be excreted by the kidneys. The total rate of glomerular filtration (glomerular filtration rate or GFR) for the whole body (i.e., for all of the nephrons in both kidneys) is normally about 125 ml per minute. That is, about 125 ml of water and dissolved substances are filtered out of the blood per minute. The following calculations may help you visualize how enormous this volume is. The GFR per hour is:
125 ml/min X 60min/hr= 7500 ml/hr.
The GFR per day is:
7500 ml/hr X 24 hr/day = 180,000 ml/day or 180 liters/day.
Now, see if you can calculate how many gallons of water we are talking about. Here are some conversion factors for you to consider: 1 quart = 960 ml, 1 liter = 1000 ml, 4 quarts. = 1 gallon. Remember to cancel units and you will have no problem.
Now, what we have just calculated is the amount of water that is removed from the blood each day - about 180 liters per day. (Actually it also includes other chemicals, but the vast majority of this glomerular filtrate is water.) Imagine the size of a 2-liter bottle of soda pop. About 90 of those bottles equals 180 liters! Obviously no one ever excretes anywhere near 180 liters of urine per day! Why? Because almost all of the estimated 43 gallons of water (which is about the same as 180 liters - did you get the right answer?) that leaves the blood by glomerular filtration, the first process in urine formation, returns to the blood by the second process - reabsorption.
Reabsorption, by definition, is the movement of substances out of the renal tubules back into the blood capillaries located around the tubules (called the peritubular copillaries). Substances reabsorbed are water, glucose and other nutrients, and sodium (Na+) and other ions. Reabsorption begins in the proximal convoluted tubules and continues in the loop of Henle, distal convoluted tubules, and collecting tubules (Figure 3). Let's discuss for a moment the three main substances that are reabsorbed back into the bloodstream.
Large amounts of water - more than 178 liters per day - are reabsorbed back into the bloodstream from the proximal tubules because the physical forces acting on the water in these tubules actually push most of the water back into the blood capillaries. In other words, about 99% of the 180 liters of water that leave the blood each day by glomerular filtration returns to the blood from the proximal tubule through the process of passive reabsorption.
The nutrient glucose (blood sugar) is entirely reabsorbed back into the blood from the proximal tubules. In fact, it is actively transported out of the tubules and into the peritubular capillary blood. None of this valuable nutrient is wasted by being lost in the urine. However, even when the kidneys are operating at peak efficiency, the nephrons can reabsorb only so much sugar and water. Their limitations are dramatically illustrated in cases of diabetes mellitus, a disease which causes the amount of sugar in the blood to rise far above normal. As already mentioned, in ordinary cases all the glucose that seeps out through the glomeruli into the tubules is reabsorbed into the blood. But if too much is present, the tubules reach the limit of their ability to pass the sugar back into the bloodstream, and the tubules retain some of it. It is then carried along in the urine, often providing a doctor with her first clue that a patient has diabetes mellitus. The value of urine as a diagnostic aid has been known to the world of medicine since as far back as the time of Hippocrates. Since then, examination of the urine has become a regular procedure for physicians as well as scientists.
Sodium ions (Na+) and other ions are only partially reabsorbed from the renal tubules back into the blood. For the most part, however, sodium ions are actively transported back into blood from the tubular fluid. The amount of sodium reabsorbed varies from time to time; it depends largely on how much salt we take in from the foods that we eat. (As stated earlier, sodium is a major component of table salt, known chemically as sodium chloride.) As a person increases the amount of salt taken into the body, that person's kidneys decrease the amount of sodium reabsorption back into the blood. That is, more sodium is retained in the tubules. Therefore, the amount of salt excreted in the urine increases. The process works the other way as well. The less the salt intake, the greater the amount of sodium reabsorbed back into the blood, and the amount of salt excreted in the urine decreases.
Now, let's describe the third important process in the formation of urine. Secretion is the process by which substances move into the distal and collecting tubules from blood in the capillaries around these tubules (Figure 3). In this respect, secretion is reabsorption in reverse. Whereas reabsorption moves substances out of the tubules and into the blood, secretion moves substances out of the blood and into the tubules where they mix with the water and other wastes and are converted into urine. These substances are secreted through either an active transport mechanism or as a result of diffusion across the membrane. Substances secreted are hydrogen ions (H+), potassium ions (K+), ammonia (NH3), and certain drugs. Kidney tubule secretion plays a crucial role in maintaining the body's acid-base balance, another example of an important body function that the kidney participates in

1 comment:

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