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Renal PhysiologyPART ONERenal Physiology Overview

PART TWORenal Clearance

PART THREERenal Acid-Base Balance

Role of the kidney in maintaining water, electrolytes, and pH balance

Plasma leaks out of the capillaries in the glomerulus. The kidneys return the nutrients to the plasma, while removing the waste products. This also maintains the pH balance, since some of the wastes are acids and bases.

Under the direction of aldosterone, they keep the balance between electrolytes, especially sodium and potassium.

This keeps the plasma volume constant to maintain BP.

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Role of Kidneys

The kidneys can adjust blood volume, blood pressure, and blood composition

BLOOD VOLUMEAdjusts the volume of water lost in urine by

responding to ADH, aldosterone, and renin BLOOD PRESSURE

Releasing renin and adenosine (increases blood pressure)

BLOOD COMPOSITIONReleasing erythropoietin (increases RBC

production)

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Sympathetic Nervous System Effect on Kidneys

Decreases the rate of blood flow (and therefore, the pressure) to the glomerulus by telling the precapillary sphincters to contract.

Sympathetic nervous system is stimulated by renin, which is released by the kidney.

Causes changes in water and sodium reabsorption by the nephron

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Hypothalamus

The hypothalamus monitors the concentration of water in the plasma.

If the plasma is too concentrated (high osmotic pressure), it means there are many electrolytes and not enough water inside the blood vessels (the person is dehydrated, and blood pressure will drop).

Since water goes to the area that has the most particles (particles SUCK water!), water will be drawn out of the nearby cells, which will cause them to shrink.

If the plasma is too dilute (low osmotic pressure), it means there is too much water and too few electrolytes inside the blood vessels (the person is over-hydrated, and blood pressure will rise).

Water will be drawn out of the blood vessels to enter the nearby cells (causing them to swell) or the space between them (interstitial space, causing edema).

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Video

Osmotic Pressurehttp://www.showme.com/sh/?h=P2a0

rWi

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Hypothalamus and Adrenal Gland When a person is dehydrated and has low blood pressure, the

hypothalamus will sense that the osmotic pressure of the plasma is too high (above homeostatic levels; plasma is too concentrated: too many electrolytes and not enough water is in the plasma), it tells the pituitary gland to release ADH (antidiuretic hormone) to cause the kidneys to retain additional water to dilute the plasma. This will make the low blood pressure go back up.

The adrenal cortex will also release aldosterone, which causes sodium ions to be reabsorbed by the kidneys, and water will follow. This will also increase the plasma volume (which will dilute it), and also help the low blood pressure to go back up.

If the osmotic pressure is too low (plasma is too dilute: too much water and not enough electrolytes in the plasma), ADH and aldosterone are not released, and excess water will pass out of the body as urine. This will make the high blood pressure go back down.

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Quiz Yourself

What does it mean when the osmotic pressure is too high? Too low?What are the causes of each of these situations?How does the body compensate for each of

these situations? What does it mean when the plasma is too dilute?

Too concentrated?What are the causes of each of these situations?How does the body compensate for each of

these situations?

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pH Imbalances

Many things can alter the pH of the bloodBeverages we drinkAcids produced by metabolismBreathing rateVomiting (loss of acid)Diarrhea (loss of base)

pH imbalances are dangerous because many enzymes only function within a narrow pH range.

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Basic Mechanisms of Urine Formation

1) Glomerular filtration 2) Tubular reabsorption 3) Tubular secretion4) Excretion

How do we determine these rates?

Master formula

Renal Physiology

Glomerular Filtration

The capillaries in the glomerulus contain many holes, called fenestrations. As blood passes through the glomerulus, the plasma passes through the fenestrations. Proteins and other large substances do not cross through; they stay in the bloodstream.

The filtered plasma leaves the bloodstream in this way, and enters the glomerular capsule, and then enters the proximal convoluted tubule.

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Glomerular Filtration In a sprinkler hose, the higher the water pressure, the faster the water

squirts through its holes. The same process is also true for the glomerulus. The blood pressure inside the glomerulus affects how fast the fluid can

filter through the fenestrations. Therefore, blood pressure affects the glomerular filtration rate (GFR). The higher the blood pressure, the higher the GFR.

The pre-capillary sphincters can also control how much pressure is in the glomerulus, much like the water faucet controls the pressure in a hose.

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Glomerular Filtration Rate GFR is used as a measure of kidney function. Normal GFR is 125 ml per minute for both kidneys

combined. That means 7.5 liters per hour, or 180 liters per day. That is 45 gallons of filtrate produced per day! Of course, most of that is reabsorbed. Average urine output is about 1.2 liters per day. That means you need to drink 1.2 liters of fluid per day

(remember that caffeine and alcohol are diuretics, so you need more than that to compensate if you drink those beverages). You need to drink more (about 2 liters per day) if you are getting a cold or flu.

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Altering GFR

Several different mechanisms can change the diameter of the afferent and efferent arterioles to alter the GFR:

Hormonal (hormones)Autonomic (nervous system)Autoregulation or local (smooth

muscle sphincters around the arterioles or capillaries near the glomerulus)

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Remember the route the fluid takes:Glomerulus Proximal convoluted tubule (PCT) Descending limb of LOH Ascending limb of LOH Distal Convoluted tubule (DCT) Collecting duct (CT)

Tubular Reabsorption This is the process by which substances in the renal tubules are

transferred back into the bloodstream. Reabsorption is the removal of water and solute molecules from filtrate after it enters the renal tubules.

Fluid goes from the glomerulus to the proximal convoluted tubule (PCT), down the loop of Henle and back up, then into the distal convoluted tubule (DCT), and into the collecting duct.

In the PCT, the nutrients are reabsorbed. If there are more nutrients than can be reabsorbed (such as excess sugar), it will be excreted in the urine.

When the nutrients are reabsorbed (in the PCT), the inside of the tubule will have more water and less nutrients. Since water goes to the area that has a higher concentration of particles (osmosis), water will also leave the tubules; this occurs mostly in the PCT.

By the time the fluid has reached the collecting duct, nothing but waste products are left, such as urea, ammonia, and bilirubin.

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Tubular Reabsorption

Capillaries follow the renal tubules and wrap around them.

The straight capillaries that travel longitudinally next to the tubules are called vasa recta, and the capillaries that wrap around the tubule are called peritubular capillaries.

There is a space between the capillaries and the tube, called the peritubular space.

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Lumen of Tubule

Tubular Cells

Filtrate arriving from Bowman’s Capsule

Peritubular Capillaries

Tubular Reabsorption

The peritubular capillaries are nearby, and the particle concentration is high inside of them. Therefore, the water in the peritubular space (lower concentration of particles) will leave that space and enter into the peritubular capillaries by osmosis.

That is how the nutrients are reabsorbed from the tubules back into the bloodstream.

Tubular Reabsorption The ascending limb of the Loop of Henle and the DCT are

impermeable to water unless hormones cause substances to be moved through their walls.

If the blood is low in sodium, (after excessive sweating), aldosterone (from the adrenal cortex) will cause more sodium to be pumped out of the tubule and into the peritubular space. The sodium will then enter the capillaries.

Since water follows where salt goes, whenever the body needs more water (such as dehydration), ADH is released (from the neurohypophysis = posterior pituitary). The synthetic form of ADH is vasopressin (a medicine).

Aldosterone and ADH will increase blood volume, increasing blood pressure.

These two hormones begin their action in the ascending limb and continue to work in the DCT.

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Tubular Secretion

Some substances are unable to filter through the glomerulus, but are not wanted by the body.

Examples are pollutants like pesticides, and many drugs, such as penicillin and non-steroidal anti-inflammatory drugs (NSAID’s).

As blood passes through the peritubular capillaries, those substances are moved from the capillaries directly into the PCT and DCT.

This is called tubular secretion.

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Juxtaglomerular Apparatus

The distal end of the renal tubule passes next to the glomerulus to form the juxtaglomerular apparatus (juxta means “next to”).

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Juxtaglomerular Apparatus:Alters BP and GFR by autoregulation

Two types of cells: 1) Macula densa cells 2) Juxtaglomerular cells

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Juxtaglomerular Apparatus: Macula Densa Cells

If blood pressure is too low, the macula densa releases adenosine, which causes vasoconstriction of the afferent arteriole. This will slow the GFR, so less water is lost, and blood pressure increases.

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If blood pressure is too high, the macula densa stops releasing adenosine, which allows the sphincters to relax.

This will increase GFR so more water is lost, and blood pressure decreases.

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Juxtaglomerular Apparatus: Macula Densa Cells

Juxtaglomerular cells secrete renin if the blood pressure is still too low after adenosine has caused vasoconstriction.

Renin causes more sodium to be reabsorbed, and water follows, so blood volume increases, so blood pressure increases.

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Juxtaglomerular Apparatus: Juxtaglomerular Cells

Summary of Autoregulation

The nephron can alter the blood pressure and flow into the glomerulus by autoregulation.

The JGA senses the blood pressure going into the glomerulus and the flow rate of the fluid going through the renal tubule. If the GFR is too low, the JGA (macula densa) will cause the pre-capillary sphincters on the nearby arterioles to contract, increasing blood pressure.

If that restores the desired filtration rate and flow, no further action is needed. If not, the kidneys produce the enzyme renin, which cuts angiotensinogen into A1. The lungs produce angiotensin converting enzyme (ACE), which turns A1 into A2, which constricts blood vessels, and also causes the release of aldosterone and ADH, raising the blood pressure further.

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Hormonal Regulation

If a person sweats from activity, eats very salty food, or has diarrhea, it changes the sodium and water content of the plasma.

Two hormones that affect the ascending limb of the Loop of Henle are aldosterone and antidiuretic hormone (ADH).

Adosterone is produced by the adrenal cortex and causes additional sodium ions to be pumped out of the tubule and into the bloodstream. Water comes with it by osmosis, and the blood pressure increases.

ADH is produced by the posterior pituitary gland and causes retention of additional water from the DCT and collecting ducts. Sodium is not included in this process, so the result is to dilute the plasma during dehydration from not drinking enough water.

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How Low BP is Raised:The renin-angiotensin system

When baroreceptors detect low blood pressure, the kidney releases an enzyme called renin.

In the meantime, angiotensinogen is made by the liver and released into the blood.

Renin cuts angiotensinogen into angiotensin-1 (A1), which travels through blood to the pulmonary capillary bed, where cells have angiotensin converting enzyme (ACE) that cuts A1 into A2 (the active form). Any word that ends in –ogen means it is a longer, inactive protein,

called a zymogen. To become activated, they need to be cut by an enzyme into a smaller

segment. A2 then causes vasoconstriction of the peripheral blood vessels so the

body’s blood will pool up to the core organs. Also, these high levels of A2 stimulates the adrenal cortex to make more

aldosterone, and also stimulates the posterior pituitary gland to release ADH. These events will raise the blood pressure.

When blood pressure is too high, the patient might be given an ACE inhibitor such as Captopril, or a renin inhibitor such as Aliskiren, or an A2 antagonist, such as Azilsartan.

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WATER

ADH SALT

ALDOSTERONE

RENIN ACE

ANGIOTENSINOGEN

A1

A2

Renin-Angiotensin Kit

Erythropoietin

The kidneys also monitor the oxygen content of the blood.

If O2 levels are low, the JGA releases the hormone erythropoietin to stimulate the bone marrow to produce more red blood cells.

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Neural Regulation

The kidneys receive about 22% of the blood pumped out of the heart, so that is a substantial quantity passing through the kidneys at any given time.

If there is a stressor and the sympathetic nervous system causes us to go into fight or flight mode, the skeletal muscles need to have a maximum amount of blood flow.

Neurons from the sympathetic nervous system innervate the kidneys to decrease renal blood flow during critical situations.

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Urine

Urine contains ions such as sodium, chloride, and potassium, as well as suspended solids, known as sediments, such as cells, mineral crystals, mucus threads, and sometimes bacteria.

The pH of urine is normally 4.6-8 A urinalysis can identify abnormal processes occurring in the body. Because urine is a waste product, its contents are influenced by

the foods and drinks we ingest. We may lose fluid elsewhere, such as through sweating or diarrhea,

which causes the urine to become more concentrated. Acids produced through metabolism can also change the pH of our

urine. Even changes in breathing rate can change the urine pH as excess acids or bases are excreted to maintain normal plasma pH.

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Abnormal Urinalysis

These substances should not be in the urine. When they are, it is abnormal. Glucose Blood Protein Pus Bilirubin Ketones

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Causes of abnormal UA

Glucose: diabetes mellitus Blood: bleeding in urinary tract from

infection or kidney stoneProtein: kidney disease, hypertension,

excessive exercise, pregnancyPus: bacterial infection in urinary tractBilirubin: liver malfunctionKetones: excessive breakdown of lipids

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Micturition

Urination is technically known as micturition. Once the volume in the urinary bladder exceeds 200

ml stretch receptors in its walls send impulses to the brain, indicating the need to eliminate.

When you make the decision to urinate, the parasympathetic nervous system stimulates the smooth muscle in the urinary bladder’s internal sphincter to relax.

Remember, the internal sphincter is smooth muscle (involuntary) and the external sphincter is skeletal muscle (voluntary). Both must relax for urine to exit.

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Diuretics for hypertension and congestive heart failure

Diuretics decrease plasma volume. One group of these drugs are called thiazide diuretics (such as Lasix). They inhibit the reabsorption of sodium and potassium from the renal tubule, causing more water to pass out as urine.

Compared to sodium, the homeostatic range of potassium is quite narrow. You can lose or gain much sodium without causing a problem, but you need a fairly exact amount of potassium or all your neurons can die.

Lasix (Furosemide) inhibits reabsorption of potassium more than other diuretics. Low blood levels of potassium are called hypokalemia. It is important for someone on Lasix to take potassium supplements or eat fruits or vegetables that have a lot of potassium (such as cantaloupe).

However, too much potassium from excessive supplements can have fatal side effects.

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Diuretics

Furosemide (Lasix)MannitolSpironolactoneAmilorideHydrochorothyozide

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Homeostasis

Maintaining the proper concentration of sodium and water is critical.

If the plasma is too concentrated with particles, nearby cells can shrink and lose their function.

If the plasma is too dilute, water can enter the nearby cells and cause them to expand, also decreasing their function.

This is especially dangerous in the brain. Studies have shown a close link between obesity, diabetes,

and kidney disease. Exercise helps maintain normal kidney function by increasing blood flow, and it decreases the incidence of high blood pressure. People receiving dialysis and those who have had kidney transplants especially need to exercise.

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The rest of this lecture is not on the test.

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Renal Physiology Video

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Countercurrent exchange

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You Tube Animation 1https://www.youtube.com/watch?v=XbI8eY-BeXY

You Tube Animation 2https://www.youtube.com/watch?v=AOqIlrQhqHQ

You Tube Animation 3https://www.youtube.com/watch?v=3THZeaMfuSw

Counter heat current exchange: Note the gradually declining differential and that the once hot and cold streams exit at the reversed temperature difference; the hotter entering stream becomes the exiting cooler stream and vice versa.

Countercurrent exchange

Countercurrent exchange is a mechanism occurring in nature and mimicked in industry and engineering, in which there is a crossover of some property, usually heat or some component, between two flowing bodies flowing in opposite directions to each other. The flowing bodies can be liquids, gases, or even solid powders, or any combination of those.

The maximum amount of heat or mass transfer that can be obtained is higher with countercurrent than co-current (parallel) exchange because countercurrent maintains a slowly declining concentration difference or gradient.

Countercurrent exchange, when set up in a loop (such as the Loop of Henle), can be used for building up concentrations of solutes. When set up in a loop with a buffering liquid between the incoming and outgoing fluid, and with active transport pumps, the system is called a Countercurrent multiplier, enabling a multiplied effect of many small pumps to gradually build up a large concentration in the buffer liquid.

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Countercurrent exchange

Countercurrent multiplication is where liquid moves in a loop followed by a long length of movement in opposite directions with an intermediate zone. The tube leading to the loop passively building up a gradient of solvent concentration while the returning tube has a constant small pumping action all along it, so that a gradual intensification of the heat or concentration is created towards the loop. Countercurrent multiplication has been found in the kidneys as well as in many other biological organs.

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Countercurrent exchange

Countercurrent exchange is used extensively in biological systems for a wide variety of purposes. For example, fish use it in their gills to transfer oxygen from the surrounding water into their blood, and birds use a countercurrent heat exchanger between blood vessels in their legs to keep heat concentrated within their bodies. Mammalian kidneys use countercurrent exchange to remove water from urine so the body can retain water used to move the nitrogenous waste products.

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Countercurrent multiplier 

A countercurrent multiplier is a system where fluid flows in a loop so that the entrance and exit are at similar low concentration of a dissolved substance but at the tip of the loop there is a very high concentration of that substance. The system allows the buildup of a high concentration gradually, with the use of many active transport pumps each pumping only against a very small gradient.

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The incoming flow starting at a low concentration has a semipermeable membrane with water passing to the buffer liquid via osmosis at a small gradient. There is a gradual buildup of concentration inside the loop until the loop tip where it reaches its maximum.

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In the example image, water enters at 299 mg/L (NaCL / H2O). Water passes because of a small osmotic pressure to the buffer liquid in this example at 300 mg/L (NaCL / H2O). Further up the loop there is a continued flow of water out of the tube and into the buffer, gradually raising the concentration of NaCL in the tube until it reaches 1199 mg/L at the tip. The buffer liquid between the two tubes is at a gradually rising concentration, always a bit over the incoming fluid, in our example reaching 1200 mg/L. This is regulated by the pumping action on the returning tube as explained immediately.

The tip of the loop has the highest concentration of salt (NaCL) in the incoming tube - in the example 1199 mg/L, and in the buffer 1200 mg/L. The returning tube has active transport pumps, pumping salt out to the buffer liquid at a low difference of concentrations of up to 200 mg/L more than in the tube. Thus when opposite the 1000 mg/L in the buffer liquid, the concentration in the tube is 800 and only 200 mg/L are needed to be pumped out. But the same is true anywhere along the line, so that at exit of the loop also only 200 mg/L need to be pumped.In effect, this can be seen as a gradually multiplying effect - hence the name of the phenomena: a 'countercurrent multiplier' or the mechanism: Countercurrent multiplication.

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• A circuit of fluid in the Loop of Henle - an important part of the kidneys allows for gradual buildup of the concentration of urine in the kidneys, by using active transport on the exiting nephrons. The active transport pumps need only to overcome a constant and low gradient of concentration, because of the countercurrent multiplier mechanism.

• Various substances are passed from the liquid entering the Nephrons until exiting the loop.

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• The sequence of flow is as follows:• Renal corpuscle: Liquid enters the nephron system at the

Bowman's capsule.• Proximal convoluted tubule: It then may reabsorb urea in the

thick descending limb. Water is removed from the nephrons by osmosis (and Glucose and other ions are pumped out with active transport), gradually raising the concentration in the nephrons.

• Loop of Henle Descending: The liquid passes from the thin descending limb to the thick ascending limb. Water is constantly released via osmosis. Gradually, there is a buildup of osmotic concentration, until 1200 mOsm is reached at the loop tip, but the difference across the membrane is kept small and constant.

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• For example, the liquid at one section inside the thin descending limb is at 400 mOsm while outside it's 401. Further down the descending limb, the inside concentration is 500 while outside it is 501, so a constant difference of 1 mOsm is kept all across the membrane, although the concentration inside and outside are gradually increasing.

• Loop of Henle Ascending: after the tip (or 'bend') of the loop, the liquid flows in the thin ascending limb. Salt - Sodium and Chlorine ions are pumped out of the liquid, gradually lowering the concentration in the exiting liquid, but, using the countercurrent multiplier mechanism, always pumping against a constant and small osmotic difference.

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• For example, the pumps at a section close to the bend pump out from 1000 mOsm inside the ascending limb to 1200 mOsm outside it, with a 200 mOsm across. Pumps further up the thin ascending limb, pump out from 400 mOsm into liquid at 600 mOsm, so again the difference is retained at 200 mOsm from the inside to the outside, while the concentration both inside and outside are gradually decreasing as the liquid flow advances.

• The liquid finally reaches a low concentration of 100 mOsm when leaving the thin ascending limb and passing through the thick one.

• Distal convoluted tubule: Once leaving the loop of Henle the thick ascending limb can optionally reabsorb and increase the concentration in the nephrons.

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• Collecting duct: The collecting duct receives liquid between 100 mOsm if no re-absorption is done, to 300 or above if re-absorption was used. The collecting duct may continue raising the concentration if required, by gradually pumping out the same ions as the Distal convoluted tubule, using the same gradient as the ascending limbs in the loop of Henle, and reaching the same concentration.

• Ureter: The liquid urine leaves to the Ureter.55

Renal Solutes

Amino Acids Ammonia Bicarbonate Calcium CO2 Chloride Creatine Creatinine

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Hydrogen Magnesium Nitrogen Phosphate Potassium Sodium Urea Uric Acid Urea Cycle

Amino Acids Amino acid definition and classifications Essential vs. Non-Essential Standard Amino Acids Essential vs. Non-Essential AA List Function of Standard and Non-Standard amino acids Discovery of Amino Acids Branched-chain amino acids Amino Acids in human nutrition Non-protein functions Uses in technology Biodegradable plastics Peptide bond formation Amino Acid Breakdown Deamination Deamination reactions in DNA Catabolism  57

Amino Acids

Amino acid definition and classifications Amino acids are made from an amine group (-NH2) and a

carboxylic acid group (-COOH), along with a side-chain specific to each amino acid. About 500 amino acids are known and can be classified in many ways. They can be classified according to the location of their functional groups, polarity, pH level, and side chain group type. The side-chain can make an amino acid a weak acid or a weak base, and hydrophilic if the side-chain is polar or hydrophobic if it is nonpolar.

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Amino Acids

Essential vs. Non-Essential Standard Amino Acids There are 20-22 amino acids in humans which form proteins, and are

known as "standard" amino acids. The amino acid Phenylalanine breaks down into the amino acid tryptophan, and arginine breaks down into ornithine, so some people count tryptophan and ornithine as the 21st and 22nd standard amino acids, while others just count the original 20. Nine of the standard amino acids are known as “essential” because they cannot be created from other compounds by the human body, and so must be taken in as food on a daily basis (we cannot store up any excess amino acids). The other 11 standard amino acids are called non-essential because the body can make them. There are many other amino acids that are non-standard because they do not make proteins. Many amino acids also play other critical roles in the body that are not related to protein synthesis. For example: in the brain, glutamate (glutamic acid) and gamma-amino-butyric acid ("GABA") are the main excitatory and inhibitory neurotransmitters. Proline is a major component of collagen. Glycine makes up red blood cells.

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Amino Acids

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Essential Nonessential

Histidine Alanine

Isoleucine Arginine (breaks down to ornithine)

Leucine Asparagine

Lysine Aspartic acid

Methionine Cysteine

Phenylalanine (breaks down to tyrosine) Glutamic acid (glutamate)

Threonine Glutamine

Tryptophan Glycine

Valine Proline

Serine

Tyrosine

Amino AcidsFunction of Standard amino acids The process of making proteins is called translation and involves the step-by-step addition of amino acids to a growing protein chain. The order in which the amino acids are added is read through the genetic code from an mRNA template, which is a RNA copy of one of the organism's genes. Function of Non-standard amino acidsNon-standard amino acids are those that do not make proteins (for example carnitine, GABA), or are not produced directly by the cell (for example, hydroxyproline and selenomethionine). They often function to modify proteins after they are made. For example, glutamate allows for better binding of calcium ions, and proline is critical for maintaining connective tissues. Modifications can also determine where proteins will bind, such as the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane. Some nonstandard amino acids do not modify the function of proteins. Examples include the neurotransmitter GABA. They also might occur as intermediates in the metabolic pathways for standard amino acids — for example, ornithine and citrulline occur in the urea cycle, which is part of amino acid catabolism.

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Amino Acids

Discovery of Amino Acids In the 1800’s, proteins were found to yield amino acids after enzymatic

digestion. It was therefore realized that proteins are formed when amino acids are linked together. A short protein (less than 70 amino acids in length) is called a peptide. The first amino acid was discovered in 1806, when two French chemists isolated a compound in asparagus that was subsequently named asparagine. Glycine and leucine were discovered in 1820. Cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Cystine is produced in the body from two cysteine molecules. Despite this, cysteine and cystine work differently to maintain health. Cysteine helps promote skin protection through white blood cell and collagen production and assists in the production of an antioxidant known as gluthathione, while cystine can aid in surgery recovery, hair growth, and treatment of anemia.

Amino acids are usually classified by the properties of their side-chain into four groups.

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Amino Acids

Branched-chain amino acids The phrase "branched-chain amino acids" or BCAA refers to the amino

acids having side-chains that are non-linear; these are leucine, isoleucine, and valine. Branched-chain amino acids are essential nutrients that the body obtains from proteins found in food, especially meat, dairy products, and legumes. Branched-chain amino acids are used to treat amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), brain conditions due to liver disease (chronic hepatic encephalopathy, latent hepatic encephalopathy), a movement disorder called tardive dyskinesia, a genetic disease called McArdle's disease, a disease called spinocerebellar degeneration, and poor appetite in elderly, kidney failure patients and cancer patients. Branched-chain amino acids are also used to help slow muscle wasting in people who are confined to bed. Some people use branched-chain amino acids to help symptoms of chronic fatigue syndrome and to improve concentration. Athletes use branched-chain amino acids to improve exercise performance and reduce protein and muscle breakdown during intense exercise.

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Amino Acids

In human nutrition When taken up into the human body from the diet, the standard

amino acids either are used to synthesize proteins or are oxidized to urea and carbon dioxide as a source of energy. The oxidation pathway starts with the removal of the amino group by a transaminase, the amino group is then fed into the urea cycle. The other product of transamination is a keto acid that enters the citric acid cycle. Glucogenic amino acids can also be converted into glucose, through gluconeogenesis.

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Amino Acids

Non-protein functions In humans, non-protein amino acids also have important roles as

metabolic intermediates, such as synthesizing other molecules, for example:

Tryptophan is a precursor of the neurotransmitter serotonin. Tyrosine (and its precursor phenylalanine) are precursors of the

catecholamine neurotransmitters dopamine, epinephrine and norepinephrine.

Glycine is a precursor of porphyrins such as heme Arginine is a precursor of nitric oxide. Aspartate, glycine, and glutamine are precursors of nucleotides.

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Amino Acids

Uses in technology Amino acids are used for a variety of applications in industry, but

their main use is as additives to animal feed. This is necessary, since many of the bulk components of these feeds, such as soybeans, lack some of the essential amino acids: Lysine, methionine, threonine, and tryptophan are most important in the production of these feeds. The food industry is also a major consumer of amino acids, in particular, glutamic acid, which is used as a flavor enhancer, and Aspartame as a low-calorie artificial sweetener. Some amino acids are used in the synthesis of drugs and cosmetics.

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Amino Acids

Biodegradable plastics Amino acids are under development as components of a range of

biodegradable polymers for use as environmentally friendly packaging and in medicine in drug delivery, the construction of prosthetic implants, and use of polyaspartate, a water-soluble biodegradable polymer that may have applications in disposable diapers and agriculture.

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Amino Acids

Peptide bond formation  The condensation of two amino acids to form a dipeptide through

a peptide bond. This polymerization of amino acids is what creates proteins. This condensation reaction yields the newly formed peptide bond and a molecule of water.

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Amino Acids

Amino Acid BreakdownDegradation of an amino acid often involves deamination by moving its amino group to alpha-ketoglutarate, forming glutamate. This process involves transaminase enzymes. The amino group is then removed through the urea cycle and is excreted in the form of urea. However, amino acid degradation can produce uric acid or ammonia instead. For example, serine is converted to pyruvate and ammonia. After removal of one or more amino groups, the remainder of the molecule can sometimes be used to synthesize new amino acids, or it can be used for energy by entering glycolysis or the citric acid cycle.

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Amino Acids

Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases. There are 4 types of deamination: intramolecular, resulting in the formation of unsaturated fatty acid; restorative, with formation of saturated fatty acid; hydrolytic, with formation of hydroxy carboxylic, and oxidative, with formation of a keto acid. In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are broken down if there is an excess of protein intake. The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and enzymes convert it to urea or uric acid by addition of carbon dioxide molecules in the urea cycle, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine.

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Amino Acids

Deamination reactions in DNA Spontaneous deamination of cytosine into uracil, releasing ammonia in the process. In DNA, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and not part of DNA.

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Cytosine Uracil

Amino Acids Catabolism  Catabolism of proteinogenic amino acids. Amino acids can be classified according to

the properties of their main products as either of the following: * Glucogenic, with the products having the ability to form glucose by

gluconeogenesis * Ketogenic, with the products not having the ability to form glucose. These products

may still be used for ketogenesis or lipid synthesis. * Amino acids catabolized into both glucogenic and ketogenic products.

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Ammonia

Ammonia is a compound of nitrogen and hydrogen with the formula NH3 , while ammonium is NH4. Ammonia is a colorless gas with a characteristic pungent smell. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia is also a building-block for the synthesis of many pharmaceuticals and is used in many commercial cleaning products. Although in wide use, ammonia is both caustic and hazardous. Household ammonia is a solution of NH3 in water.

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Ammonia

Natural occurrenceAmmonia is found in trace quantities in the atmosphere, being produced from the putrefaction (decay process) of animal and vegetable matter. When we consume those foods, the nitrogen is taken into our body and used to make amino acids and other important substances. When amino acids are broken down, NH3 is the toxic waste product, and has an alkaline pH. The kidneys excrete or reabsorb NH3 to keep the blood plasma at neutral pH. Dilute aqueous ammonia can be applied on the skin to lessen the effects of acidic animal venoms, such as from insects and jellyfish. The basic pH of ammonia also is the basis of its toxicity and its use as a cleaner. By creating a solution with a pH much higher than a neutral water solution, proteins (enzymes) will denature, leading to cell damage, death of the cell, and eventually death of the organism. Dirt often consists of fats and oils, which are not very soluble in water. Ammonia causes them to dissolve in water. This will allow the ammonia and water, with its dissolved dirty oils to evaporate completely, leaving a clean surface.

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Ammonia

History The Romans called the ammonium chloride deposits they collected from near the Temple of Amun in ancient Libya 'sal ammoniacus' (salt of Amun).  ToxicityThe toxicity of ammonia solutions does not usually cause problems for humans and other mammals, as a specific mechanism exists to prevent its build-up in the bloodstream. Ammonia is converted to carbamoyl phosphate by an enzyme, and then enters the urea cycle to be either incorporated into amino acids or excreted in the urine. However, fish and amphibians lack this mechanism, as they can usually eliminate ammonia from their bodies by direct excretion. Ammonia even at dilute concentrations is highly toxic to aquatic animals, and for this reason it is classified as dangerous for the environment.

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Ammonia

Formation and elimination in the bodyAmmonia is a metabolic product of amino acid deamination catalyzed by enzymes. Ammonia is quickly converted to urea, which is much less toxic, particularly less basic. This urea is a major component of the dry weight of urine. The liver converts ammonia to urea through a series of reactions known as the urea cycle. Liver dysfunction, such as that seen in cirrhosis, may lead to elevated amounts of ammonia in the blood (hyperammonemia). Likewise, defects in the enzymes responsible for the urea cycle, leads to this disorder. It causes confusion and coma, neurological problems, and aciduria (acid in the urine).

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Ammonia

Acid base balanceAmmonia is important for normal animal acid/base balance. After formation of ammonium from glutamine, α-ketoglutarate may be degraded to produce two molecules of bicarbonate, which are then available as buffers for acids. Ammonium is excreted in the urine, resulting in net acid loss. Ammonia may itself diffuse across the renal tubules, combine with a hydrogen ion, and thus allow for further acid excretion.

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Bicarbonate

Bicarbonate has the chemical formula HCO3−. Bicarbonate serves a crucial biochemical role in the physiological pH buffering system.

 

Bicarbonate participates in this equilibrium reaction.

CO2 + H2O ↔ H2CO3 ↔ HCO3− + H+

Bicarbonate is alkaline, and a vital component of the pH buffering system of the human body (maintaining acid-base homeostasis). 70-75% of CO2 in the body is converted into carbonic acid (H2CO3), which can quickly turn into bicarbonate (HCO3

−). Bicarbonate – in conjunction with water, hydrogen ions, and carbon dioxide forms a buffering system, which provides prompt resistance to drastic pH changes in both the acidic and basic directions. This is especially important for protecting tissues of the central nervous system, where pH changes too far outside of the normal range in either direction could prove disastrous. Bicarbonate also acts to regulate pH in the small intestine. It is released from the pancreas in response to the hormone secretin to neutralize the acidic chyme entering the duodenum from the stomach.

 

The most common salt of the bicarbonate ion is sodium bicarbonate, NaHCO3, which is commonly known as baking soda. When heated or exposed to an acids, such as acetic acid (vinegar), sodium bicarbonate releases carbon dioxide. This is used as a leavening agent in baking.

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CalciumCalcium is the fifth-most-abundant element by mass in the Earth's crust. Calcium is essential for living organisms, where movement of the calcium ion Ca2+ into and out of the cytoplasm functions as a signal for many cellular processes. It is the major material used in mineralization of bone, and teeth. It is the relatively high-atomic-number of calcium that causes bone to be radio-opaque (can see bone on x-rays). Of the human body's solid components after cremation, about a third of the total "mineral" mass is the approximately one kilogram of calcium that composes the average skeleton (the remainder being mostly phosphorus and oxygen). Calcium, combined with phosphate forms hydroxyapatite, which is the mineral portion of human and animal bones and teeth.

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Calcium

Calcium compounds Calcium carbonate (CaCO3) is used in manufacturing cement and

mortar, lime, limestone, and in toothpastes. Calcium hydroxide solution (Ca(OH)2) (also known as limewater) is used to

detect the presence of carbon dioxide by being bubbled through a solution. It turns cloudy where CO2 is present.

Calcium arsenate (Ca3(AsO4)2) is used in insecticides. Calcium carbide (CaC2) is used to make acetylene gas (for torches for welding)

and in the manufacturing of plastics. Calcium chloride (CaCl2) is used in ice removal and dust control on dirt roads,

in conditioner for concrete, as an additive in canned tomatoes, and to provide body for automobile tires.

Calcium cyclamate (Ca(C6H11NHSO3)2) is used as a sweetening agent in several countries. In the United States it is no longer permitted for use because of suspected cancer-causing properties.

Calcium gluconate (Ca(C6H11O7)2) is used as a food additive and in vitamin pills.

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Calcium Calcium compounds Calcium hypochlorite (Ca(OCl)2) is used as a swimming pool disinfectant, as

a bleaching agent, as an ingredient in deodorant, and in algaecide and fungicide. Calcium permanganate (Ca(MnO4)2) is used in liquid rocket propellant, and as a

water sterilizing agent and in dental procedures. Calcium phosphate (Ca3(PO4)2) is used as a supplement for animal feed, fertilizer, in

commercial production for dough and yeast products, in the manufacture of glass, and in dental products.

Calcium phosphide (Ca3P2) is used in fireworks, rodenticide, torpedoes and flares. Calcium stearate (Ca(C18H35O2)2) is used in the manufacture

of wax crayons, cements, plastics and cosmetics, as a food additive, and in paints. Calcium sulfate (CaSO4·2H2O) is used as common blackboard chalk, and Plaster of

Paris. Calcium tungstate (CaWO4) is used in luminous paints, fluorescent lights and in X-

ray studies. Hydroxylapatite (Ca5(PO4)3(OH), makes up seventy percent of bone. Also

carbonated-calcium deficient hydroxylapatite is the main mineral of which dental enamel and dentin are comprised.

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Calcium

Calcium is an important component of a healthy diet and a mineral necessary for life. Approximately 99 percent of the body's calcium is stored in the bones and teeth. The rest of the calcium in the body has other important uses, such as some exocytosis, especially neurotransmitter release, and muscle contraction. In the electrical conduction system of the heart, calcium replaces sodium as the mineral that depolarizes the cell, proliferating the action potential. Long-term calcium deficiency can lead to rickets and poor blood clotting and in case of a menopausal woman, it can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. While a lifelong deficit can affect bone and tooth formation, over-retention can cause hypercalcemia (elevated levels of calcium in the blood), impaired kidney function and decreased absorption of other minerals. Several sources suggest a correlation between high calcium intake (2000 mg per day, or twice the U.S. recommended daily allowance, equivalent to six or more glasses of milk per day) and prostate cancer. High calcium intakes or high calcium absorption were previously thought to contribute to the development of kidney stones. However, a high calcium intake has been associated with a lower risk for kidney stones in more recent research. Vitamin D is needed to absorb calcium.

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Calcium

Dairy products, such as milk and cheese, are a well-known source of calcium. Some individuals are allergic to dairy products and even more people, in particular those of non Indo-European descent, are lactose-intolerant, leaving them unable to consume non-fermented dairy products in quantities larger than about half a liter per serving. Others, such as vegans, avoid dairy products for ethical and health reasons.Many good vegetable sources of calcium exist, including seaweeds such as kelp, and nuts and seeds like almonds, hazelnuts, sesame, and pistachio; molasses; beans (especially soy beans); figs; rutabaga; broccoli; dandelion leaves; and kale. In addition, some drinks are often fortified with calcium (like soy milk or orange juice).Numerous vegetables, notably spinach and rhubarb, have a high calcium content, but they may also contain varying amounts of oxalic acid that binds calcium and reduces its absorption. An overlooked source of calcium is eggshell, which can be ground into a powder and mixed into food or a glass of water.

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CalciumDietary supplements

Most experts recommend that supplements be taken with food and that no more than 600 mg should be taken at a time because the percent of calcium absorbed decreases as the amount of calcium in the supplement increases. It is recommended to spread doses throughout the day. Recommended daily calcium intake for adults ranges from 1000 to 1500 mg. It is recommended to take supplements with food to aid in absorption.

Vitamin D is added to some calcium supplements. Proper vitamin D status is important because vitamin D is converted to a hormone in the body, which then induces the synthesis of intestinal proteins responsible for calcium absorption.

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Calcium The absorption of calcium from most food and commonly used dietary

supplements is very similar. This is contrary to what many calcium supplement manufacturers claim in their promotional materials.

Calcium carbonate is the most common and least expensive calcium supplement. It should be taken with food, and depends on low pH levels (acidic) for proper absorption in the intestine.  While most people digest calcium carbonate very well, some might develop gastrointestinal discomfort or gas. Taking magnesium with it can help to avoid constipation. Calcium carbonate is 40% elemental calcium. 1000 mg will provide 400 mg of calcium. However, supplement labels will usually indicate how much calcium is present in each serving, not how much calcium carbonate is present.

Antacids frequently contain calcium carbonate, and are a commonly used, inexpensive calcium supplement.

Coral calcium is a salt of calcium derived from fossilized coral reefs. Coral calcium is composed of calcium carbonate and trace minerals.

Calcium citrate can be taken without food and is the supplement of choice for individuals with achlorhydria or who are taking histamine-2 blockers or proton-pump inhibitors due to gastric ulcers. Calcium citrate is about 21% elemental calcium. 1000 mg will provide 210 mg of calcium. It is more expensive than calcium carbonate and more of it must be taken to get the same amount of calcium. 85

Calcium Calcium phosphate costs more than calcium carbonate, but less

than calcium citrate. Microcrystalline Hydroxyapatite (MH) is one of several forms of calcium phosphate used as a dietary supplement. Hydroxyapatite is about 40% calcium.

Calcium lactate has similar absorption as calcium carbonate, but is more expensive. Calcium lactate and calcium gluconate are less concentrated forms of calcium and are not practical oral supplements.

Calcium chelates are synthetic calcium compounds in which calcium is bound to an organic molecule, such as malate, aspartate, or fumarate. These forms of calcium may be better absorbed on an empty stomach. However, in general they are absorbed similarly to calcium carbonate and other common calcium supplements when taken with food. The "chelate" mimics the action that natural food performs by keeping the calcium soluble in the intestine. Thus, on an empty stomach, in some individuals, chelates might, in theory, be absorbed better. 86

Calcium

Hazards and toxicityExcessive consumption of calcium carbonate antacids/dietary supplements (such as Tums) over a period of weeks or months can cause milk-alkali syndrome, with symptoms ranging from hypercalcemia to potentially fatal renal failure. Persons consuming more than 10 grams/day of CaCO3 (=4 g Ca) are at risk of developing milk-alkali syndrome. Oral calcium supplements diminish the absorption of thyroxine when taken within four to six hours of each other. Thus, people taking both calcium and thyroxine run the risk of inadequate thyroid hormone replacement and thence hypothyroidism if they take them simultaneously or near-simultaneously.

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Carbon dioxide

Carbon dioxide is an important greenhouse gas, warming the Earth's surface to a higher temperature by reducing outward radiation. Atmospheric carbon dioxide is the primary source of carbon in life on Earth and its concentration in Earth's pre-industrial atmosphere since late in the Precambrian eon has been regulated by photosynthetic organisms. Burning of carbon-based fuels since the industrial revolution has rapidly increased concentrations of atmospheric carbon dioxide, increasing the rate of global warming and causing anthropogenic climate change. It is also a major source of ocean acidification since it dissolves in water to form carbonic acid, which is a weak acid as its ionization in water is incomplete. CO2 + H2O    H2CO3

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Carbon dioxide

HistoryCarbon dioxide was one of the first gases to be described as a substance distinct from air. In the seventeenth century, the Flemish chemist Jan Baptist van Helmont observed that when he burned charcoal in a closed vessel, the mass of the resulting ash was much less than that of the original charcoal. His interpretation was that the rest of the charcoal had been transmuted into an invisible substance he termed a "gas" or "wild spirit" (spiritus sylvestre). Carbon dioxide is used by the food industry, the oil industry, and the chemical industry.  

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Carbon dioxide

Foods A candy called Pop Rocks is pressurized with carbon dioxide gas. Leavening agents cause dough to rise by producing carbon dioxide. Baker's yeast produces carbon dioxide by fermentation of sugars within the dough, while chemical leaveners such as baking powder and baking soda release carbon dioxide when heated or if exposed to acids.Beverages Carbon dioxide is used to produce carbonated soft drinks and soda water. Traditionally, the carbonation in beer and sparkling wine came about through natural fermentation, but many manufacturers carbonate these drinks with carbon dioxide recovered from the fermentation process.

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Carbon dioxide

Wine making Carbon dioxide in the form of dry ice is often used in the wine making process to cool down bunches of grapes quickly after picking to help prevent spontaneous fermentation by wild yeast. The main advantage of using dry ice over regular water ice is that it cools the grapes without adding any additional water that may decrease the sugar concentration in the grape, and therefore also decrease the alcohol concentration in the finished wine.Biological applications In medicine, up to 5% carbon dioxide (130 times atmospheric concentration) is added to oxygen for stimulation of breathing after apnea and to stabilize theO2/CO2 balance in blood.It has been proposed that carbon dioxide from power generation be bubbled into ponds to grow algae that could then be converted into biodiesel fuel.

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Carbon dioxide

Biological role Carbon dioxide is an end product in organisms that obtain energy from breaking down sugars, fats and amino acids with oxygen as part of their metabolism, in a process known as cellular respiration. This includes all plants, animals, many fungi and some bacteria. In higher animals, the carbon dioxide travels in the blood from the body's tissues to the lungs where it is exhaled. In plants using photosynthesis, carbon dioxide is absorbed from the atmosphere.

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Carbon dioxide

ToxicityAcute carbon dioxide physiological effect is hypercapnia or asphyxiation sometimes known by the names given to it by miners: blackdamp. Blackdamp is primarily nitrogen and carbon dioxide and kills via suffocation (having displaced oxygen). Miners would try to alert themselves to dangerous levels of blackdamp and other gases in a mine shaft by bringing a caged canary with them as they worked. The canary is more sensitive to environmental gases than humans and as it became unconscious would stop singing and fall off its perch. The Davy lamp could also detect high levels of blackdamp (which collect near the floor) by burning less brightly, while methane, another suffocating gas and explosion risk would make the lamp burn more brightly).

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Carbon dioxide

Human physiology The body produces approximately 2.3 pounds (1 kg) of carbon dioxide per day per person, containing 0.63 pounds (290 g) of carbon. In humans, this carbon dioxide is carried through the venous system and is breathed out through the lungs. Therefore, the carbon dioxide content in the body is high in the venous system, and decreases in the respiratory system, resulting in lower levels along any arterial system. Carbon dioxide content in this sense is often given as the partial pressure, which is the pressure which carbon dioxide would have had if it alone occupied the volume.

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Carbon dioxide

Transport in the blood CO2 is carried in blood in three different ways.

70% to 80% is converted to bicarbonate ions HCO3− by the

enzyme carbonic anhydrase in the red blood cells, by the reaction CO2 + H2O → H2CO3 → H+ + HCO3

−

5% – 10% is dissolved in the plasma5% – 10% is bound to hemoglobin Hemoglobin, the main oxygen-carrying molecule in red blood cells, carries both oxygen and carbon dioxide. However, the CO2 bound to hemoglobin does not bind to the same site as oxygen. Instead, it combines with the N-terminal groups on the four globin chains. However, because of its effects on the hemoglobin molecule, the binding of CO2 decreases the amount of oxygen that is bound for a given partial pressure of oxygen. The decreased binding to carbon dioxide in the blood due to increased oxygen levels is known as the Haldane Effect, and is important in the transport of carbon dioxide from the tissues to the lungs. Conversely, a rise in the partial pressure of CO2 or a lower pH will cause offloading of oxygen from hemoglobin, which is known as the Bohr Effect.

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Carbon dioxide

Regulation of respiration Carbon dioxide is one of the mediators of local autoregulation of blood supply. If its levels are high, the capillaries expand to allow a greater blood flow to that tissue.Bicarbonate ions are crucial for regulating blood pH. A person's breathing rate influences the level of CO2 in their blood. Breathing that is too slow or shallow causes respiratory acidosis, while breathing that is too rapid leads to hyperventilation, which can cause respiratory alkalosis.

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Carbon dioxide

Regulation of respiration Although the body requires oxygen for metabolism, low oxygen levels normally do not stimulate breathing. Rather, breathing is stimulated by higher carbon dioxide levels. As a result, breathing low-pressure air or a gas mixture with no oxygen at all (such as pure nitrogen) can lead to loss of consciousness without ever experiencing air hunger. This is especially perilous for high-altitude fighter pilots. It is also why flight attendants instruct passengers, in case of loss of cabin pressure, to apply the oxygen mask to themselves first before helping others; otherwise, one risks losing consciousness.

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Carbon dioxide

Regulation of respiration The respiratory centers try to maintain an arterial CO2 pressure of 40 mm Hg. With intentional hyperventilation, the CO2 content of arterial blood may be lowered to 10–20 mm Hg (the oxygen content of the blood is little affected), and the respiratory drive is diminished. This is why one can hold one's breath longer after hyperventilating than without hyperventilating. This carries the risk that unconsciousness may result before the need to breathe becomes overwhelming, which is why hyperventilation is particularly dangerous before free diving.

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Chloride

The chloride ion and its salts, such as sodium chloride, are very soluble in water. It is an essential electrolyte located in all body fluids responsible for maintaining acid/base balance, transmitting nerve impulses and regulating fluid in and out of cells. The amount of chloride in the blood is carefully controlled by the kidneys. Chloride is used to form salts that can preserve food such as sodium chloride. Other salts such as calcium chloride, magnesium chloride, potassium chloride have varied uses ranging from medical treatments to cement formation.

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Creatine

Not to be confused with creatinine.Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of ATP. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle, which he later named after the Greek word for meat (kreas). In solution, creatine is in equilibrium with creatinine.

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Creatine

Biosynthesis Creatine is naturally produced in the human body from amino acids primarily in the kidney and liver. It is transported in the blood for use by muscles. Approximately 95% of the human body's total creatine is located in skeletal muscle. Creatine is not an essential nutrient, as it can be manufactured in the human body from arginine, glycine, and methionine. In humans and animals, approximately half of stored creatine originates from food (about 1 g/day, mainly from meat). Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.

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Creatine

The phosphocreatine system Creatine, synthesized in the liver and kidney, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2-5 mM, which would result in a muscle contraction of only a few seconds. Fortunately, during times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (CK).

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Creatine

Use as a supplement Creatine supplements are used by athletes, bodybuilders, wrestlers, sprinters, and others who wish to gain muscle mass, typically consuming 2 to 3 times the amount that could be obtained from a very-high-protein diet. The Mayo Clinic states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies to creatine.

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Creatine

Use as a supplement There are reports of kidney damage with creatine use, such as nephritis; patients with kidney disease should avoid use of this supplement. In similar manner, liver function may be altered, and caution is advised in those with underlying liver disease. Long-term administration of large quantities of creatine is reported to increase the production of formaldehyde, which has the potential to cause serious unwanted side-effects. In 2004 the European Food Safety Authority (EFSA) published a record which stated that oral long-term intake of 3g pure creatine per day is risk-free. Other research has shown that oral creatine supplementation at a rate of 5 to 20 grams per day appears to be very safe and largely devoid of adverse side-effects, while at the same time effectively improving the physiological response to resistance exercise, increasing the maximal force production of muscles in both men and women.

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Creatine

Pharmacokinetics To maintain an elevated plasma level it is necessary to take small oral doses every 3–6 hours throughout the day. After the "loading dose" period (1–2 weeks, 12-24 g a day), it is no longer necessary to maintain a consistently high serum level of creatine. Creatine is consumed by the body fairly quickly, and if one wishes to maintain the high concentration of creatine, Post-loading dose, 2-5 g daily is the standard amount to intake.

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Creatine

Treatment of diseases Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders. Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (arthritis, congestive heart failure, Parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, and neuroprotection), and depression.

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Creatine

Improved cognitive ability A placebo-controlled double-blind experiment found that a group of subjects composed of vegetarians and vegans who took 5 grams of creatine per day for six weeks showed a significant improvement on two separate tests of fluid intelligence, Raven's Progressive Matrices, and the backward digit span test from the WAIS. The treatment group was able to repeat longer sequences of numbers from memory and had higher overall IQ scores than the control group. The researchers concluded that "supplementation with creatine significantly increased intelligence compared with placebo." A subsequent study found that creatine supplements improved cognitive ability in the elderly. A study on young adults (0.03 g/kg/day for six weeks, e.g., 2 g/day for a 70-kilogram (150 lb) individual) failed to find any improvements. Perhaps this improvement is only seen in those who are creatine deficient.

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Creatine

Creatine phosphate (CP) or PCr (Pcr), also known as Phosphocreatine, is a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle and the brain.

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Creatine

Chemistry Phosphocreatine is formed from parts of three amino acids: arginine (Arg), glycine (Gly), and methionine (Met). It can be synthesized by formation of guanidinoacetate from Arg and Gly (in kidney) followed by methylation (S-adenosyl methionine is required) to creatine (in liver), and phosphorylation by creatine kinase (ATP is required) to phosphocreatine (in muscle); catabolism: dehydration to form the cyclic Schiff base creatinine. Phosphocreatine is synthesized in the liver and transported to the muscle cells, via the bloodstream, for storage. The creatine phosphate shuttle facilitates transport of high energy phosphate from mitochondria.

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Creatine

Function Phosphocreatine can anaerobically donate a phosphate group to ADP to form ATP during the first 2 to 7 seconds following an intense muscular or neuronal effort. Conversely, excess ATP can be used during a period of low effort to convert creatine to phosphocreatine. The reversible phosphorylation of creatine (i.e., both the forward and backward reaction) is catalyzed by several creatine kinases. The presence of creatine kinase (CK-MB, MB for muscle/brain) in blood plasma is indicative of tissue damage and is used in the diagnosis of myocardial infarction.

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Creatine

Function The cell's ability to generate phosphocreatine from excess ATP during rest, as well as its use of phosphocreatine for quick regeneration of ATP during intense activity, provides a spatial and temporal buffer of ATP concentration. In other words, phosphocreatine acts as high-energy reserve in a coupled reaction; the energy given off from donating the phosphate group is used to regenerate the other compound - in this case, ATP. Phosphocreatine plays a particularly important role in tissues that have high, fluctuating energy demands such as muscle and brain.

112

Creatinine

Creatinine (from the Greek “flesh”) is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass).

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Creatinine

Biological relevance Serum creatinine (a blood measurement) is an important indicator of renal health because it is an easily-measured by-product of muscle metabolism. Creatinine itself is an important biomolecule because it is a major by-product of energy usage in muscle, via a biological system involving creatine, phosphocreatine (also known as creatine phosphate), and adenosine triphosphate (ATP, the body's immediate energy supply).

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Creatinine

Biological relevance Creatine is primarily synthesized in the liver. It is then transported through blood to the other organs, muscle, and brain where it is converted into the high energy compound phosphocreatine. Creatinine is chiefly filtered out of the blood by the kidneys (glomerular filtration and proximal tubular secretion). There is little or no tubular reabsorption of creatinine. If the filtering of the kidney is deficient, creatinine blood levels rise. Therefore, creatinine levels in blood and urine may be used to calculate the creatinine clearance (CrCl), which reflects the glomerular filtration rate (GFR).

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Creatinine

Biological relevance The GFR is clinically important because it is a measurement of renal function. A more complete estimation of renal function can be made when interpreting the blood (plasma) concentration of creatinine along with that of urea. BUN-to-creatinine ratio (the ratio of blood urea nitrogen to creatinine) can indicate other problems besides those intrinsic to the kidney; for example, a urea level raised out of proportion to the creatinine may indicate a pre-renal problem such as volume depletion.

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Creatinine

Diagnostic use Serum creatinine Measuring serum creatinine is a simple test and it is the most commonly used indicator of renal function. A rise in blood creatinine level is observed only with marked damage to functioning nephrons. Therefore, this test is unsuitable for detecting early-stage kidney disease. A better estimation of kidney function is given by the creatinine clearance (CrCl) test. Creatinine clearance can be accurately calculated using serum creatinine concentration and some or all of the following variables: sex, age, weight and race, as suggested by the American Diabetes Association without a 24-hour urine collection.

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Creatinine

Urine creatinine Creatinine concentration is also checked during standard urine drug tests. Normal creatinine levels indicate the test sample is undiluted, whereas low amounts of creatinine in the urine indicate either a manipulated test or low individual baseline creatinine levels. Test samples considered manipulated due to low creatinine are not tested, and the test is sometimes considered failed.

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Creatinine

Urine creatinine Diluted samples may not always be due to a conscious effort of subversion, and diluted samples cannot be proved to be intentional, but are only assumed to be. Diuretics, such as coffee and tea, cause more frequent urination, thus potently decreasing creatinine levels. They are usually used with other tests to reference levels of other substances measured in the urine. A decrease in muscle mass will also cause a lower reading of creatinine, as will pregnancy.

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Creatinine

Interpretation The trend of serum creatinine levels over time is more important than absolute creatinine level.Creatinine levels may increase when ACE inhibitors (ACEI) or angiotensin II receptor antagonists (or angiotensin receptor blockers, ARBs) are taken. Using both ACEI and ARB concomitantly will increase creatinine levels to a greater degree than either of the two drugs would individually. An increase of <30% is to be expected with ACEI or ARB use.

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Hydrogen

Hydrogen is a chemical element with chemical symbol H and atomic number 1. It is the most abundant chemical substance, constituting roughly 75% of the Universe's mass. It readily forms covalent (shares an electron orbital) bonds with most non-metallic elements.

Hydrogen plays a particularly important role in acid-base chemistry with many reactions exchanging protons between soluble molecules.

Protons and acids Oxidation of hydrogen removes its electron and gives H+,

which contains no electrons and a nucleus which is usually composed of one proton. Acids are proton donors, while bases are proton acceptors.

A bare proton, H+, cannot exist in solution or in ionic crystals, because of its unstoppable attraction to other atoms or molecules with electrons. 121

Hydrogen

HistoryIn 1671, Robert Boyle discovered and described the reaction between iron filings and dilute acids, which results in the production of hydrogen gas. In 1766,Henry Cavendish was the first to recognize hydrogen gas as a discrete substance, by naming the gas from a metal-acid reaction "flammable air". He is usually given credit for its discovery as an element. In 1783, Antoine Lavoisier gave the element the name hydrogen (from the Greek hydro meaning water and  genes meaning creator) when he and Laplace reproduced Cavendish's finding that water is produced when hydrogen is burned.

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Hydrogen

ApplicationsH2 has several other important uses. H2 is used as a hydrogenating agent, particularly in increasing the level of saturation of unsaturated fats and oils (found in items such as margarine), and in the production of methanol. Energy carrierHydrogen is not an energy resource, except in the hypothetical context of commercial nuclear fusion power plants using deuterium or tritium, a technology presently far from development. The Sun's energy comes from nuclear fusion of hydrogen, but this process is difficult to achieve controllably on Earth. Elemental hydrogen from solar, biological, or electrical sources require more energy to make it than is obtained by burning it, so in these cases hydrogen functions as an energy carrier, like a battery. Hydrogen may be obtained from fossil sources (such as methane), but these sources are unsustainable.123

Hydrogen

Biological reactionsH2 is a product of some types of anaerobic metabolism and is produced by several microorganisms, usually via reactions catalyzed by enzymes called hydrogenases. These enzymes catalyze the reversible redox reaction between H2 and its component two protons and two electrons. Creation of hydrogen gas occurs in the transfer of reducing equivalents produced during pyruvate fermentation to water.

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Hydrogen

Biological reactionsWater splitting, in which water is decomposed into its component protons, electrons, and oxygen, occurs in the light reactions in all photosynthetic organisms. Some such organisms, including the alga Chlamydomonas reinhardtii and cyanobacteria, have evolved a second step in the dark reactions in which protons and electrons are reduced to form H2 gas by specialized hydrogenases in the chloroplast. Efforts have been undertaken to genetically modify cyanobacterial hydrogenases to efficiently synthesize H2 gas even in the presence of oxygen. Efforts have also been undertaken with genetically modified alga in a bioreactor.

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Magnesium

Magnesium is a chemical element with the symbol Mg and atomic number 12. Its common oxidation number is +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole. Magnesium is the fourth most common element in the Earth as a whole (behind iron, oxygen and silicon), making up 13% of the planet's mass. Due to magnesium ion's high solubility in water, it is the third most abundant element dissolved in seawater.

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Magnesium

The free metal burns with a characteristic brilliant white light, making it a useful ingredient in flares. The metal is now mainly obtained by electrolysis of seawater. In human biology, magnesium is the eleventh most abundant element by mass in the human body. Its ions are essential to all living cells, where they play a major role in manipulating important biological polyphosphate compounds like ATP, DNA, and RNA. Hundreds of enzymes thus require magnesium ions to function. Magnesium compounds are used medicinally as common laxatives, antacids (e.g., milk of magnesia), and in a number of situations where stabilization of abnormal nerve excitation and blood vessel spasm is required (e.g., to treat eclampsia). In vegetation, magnesium is the metallic ion at the center of chlorophyll, and is thus a common additive to fertilizers.

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MagnesiumHistory The name magnesium originates from the Greek word for a district in Thessaly called Magnesia. It is related to magnetite and manganese, which also originated from this area, and required differentiation as separate substances. Magnesium is the eighth most abundant element in the Earth's crust by mass. In 1618, a farmer at Epsom in England attempted to give his cows water from a well there. The cows refused to drink because of the water's bitter taste, but the farmer noticed that the water seemed to heal scratches and rashes. The substance became known as Epsom salts and its fame spread. It was eventually recognized as hydrated magnesium sulfate.

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Biological role Because of the important interaction between phosphate and magnesium ions, magnesium ions are essential to the basic nucleic acid chemistry of life, and thus are essential to all cells of all known living organisms. Over 300 enzymes require the presence of magnesium ions for their catalytic action, including all enzymes utilizing or synthesizing ATP, or those that use other nucleotides to synthesize DNA and RNA. ATP exists in cells normally as a chelate of ATP and a magnesium ion. Plants have an additional use for magnesium in that chlorophylls are magnesium-centered porphyrins. Magnesium deficiency in plants causes late-season yellowing between leaf veins, especially in older leaves, and can be corrected by applying Epsom salts (which is rapidly leached).

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Biological role Magnesium is a vital component of a healthy human diet. Human magnesium deficiency (including conditions that show few overt symptoms) is relatively rare, although only 32% of people in the United States meet the RDA-DRI; low levels of magnesium in the body has been associated with the development of a number of human illnesses such as asthma, diabetes, and osteoporosis. Taken in the proper amount, magnesium plays a role in preventing both stroke and heart attack. The symptoms of people with fibromyalgia, migraines, and girls going through their premenstrual syndrome are less severe and magnesium can shorten the length of the migraine symptoms.

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Biological role Adult human bodies contain about 24 grams of magnesium, with 60% in the skeleton, 39% intracellular (20% in skeletal muscle), and 1% extracellular. Serum magnesium levels may appear normal even in cases of underlying intracellular deficiency, although no known mechanism maintains a homeostatic level in the blood other than renal excretion of high blood levels.

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Biological role Intracellular magnesium is correlated with intracellular potassium. Magnesium is absorbed in the gastrointestinal tract, with more absorbed when status is lower. In humans, magnesium appears to facilitate calcium absorption. Low and high protein intake inhibit magnesium absorption, and other factors such as phosphate and fat affect absorption. Absorbed dietary magnesium is largely excreted through the urine, although most magnesium "administered orally" is excreted through the feces. Magnesium status may be assessed roughly through serum and erythrocyte Mg concentrations and urinary and fecal excretion, but intravenous magnesium loading tests are likely the most accurate and practical in most people. In these tests, magnesium is injected intravenously; a retention of 20% or more indicates deficiency. Other nutrient deficiencies are identified through biomarkers, but none are established for magnesium.

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Biological role Spices, nuts, cereals, coffee, cocoa, tea, and vegetables are rich sources of magnesium. Green leafy vegetables such as spinach are also rich in magnesium as they contain chlorophyll. Observations of reduced dietary magnesium intake in modern Western countries compared to earlier generations may be related to food refining and modern fertilizers that contain no magnesium.

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Excess magnesium in the blood is freely filtered at the kidneys, and for this reason it is difficult to overdose on magnesium from dietary sources alone. With supplements, overdose is possible, however, particularly in people with poor renal function; occasionally, with use of high cathartic doses of magnesium salts, severe hypermagnesemia has been reported to occur even without renal dysfunction. Alcoholism can produce a magnesium deficiency, which is easily reversed by oral or parenteral administration, depending on the degree of deficiency.

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Detection in biological fluids Magnesium concentrations in plasma or serum may be measured to monitor for efficacy and safety in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. The newborn children of mothers who received parenteral magnesium sulfate during labor may exhibit toxicity at serum magnesium levels that were considered appropriate for the mothers.

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Magnesium in treatment-resistant depression (TRD) There has been some speculation that magnesium deficiency can lead to depression. Cerebral spinal fluid (CSF) magnesium has been found low in treatment-resistant suicidal depression and in patients that have attempted suicide. Brain magnesium has been found low in TRD using phosphorus nuclear magnetic resonance spectroscopy, an accurate means for measuring brain magnesium. Blood and CSF magnesium do not appear well-correlated with major depression. Magnesium chloride in relatively small doses was found as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily.

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Magnesium in disease Results from a meta-analysis of randomized clinical trials demonstrated that magnesium supplementation lowers high blood pressure in a dose dependent manner. Low serum magnesium levels are associated with metabolic syndrome, diabetes mellitus type 2 and hypertension. Magnesium therapy is recommended for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death as well as for the treatment of patients with digoxin intoxication-induced arrhythmias.

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Magnesium in disease Magnesium is also the drug of choice in the management of pre-eclampsia and eclampsia. Besides its therapeutic role, magnesium has an additional beneficial effect on calcification. Patients with chronic kidney disease have a high prevalence of vascular calcification, and cardiovascular disease is the leading cause of death in this population. Magnesium is a natural calcium antagonist and low circulating magnesium levels are associated with vascular calcification.

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Magnesium in disease Magnesium supplementation might be useful in reducing the progression of atherosclerosis in chronic dialysis patients. Low serum magnesium may be an independent risk factor for death in patients with chronic kidney disease, and patients with mildly elevated serum magnesium levels could have a survival advantage over those with lower magnesium levels.

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Nitrogen

Nitrogen is a chemical element with symbol N and atomic number 7. Elemental nitrogen is a colorless, odorless, tasteless gas, constituting 78% by volume of Earth's atmosphere. The element nitrogen was discovered as a separable component of air, by Scottish physician Daniel Rutherford, in 1772. Nitrogen is a common element in the universe, estimated at about seventh in total abundance in our galaxy and the Solar System. It is synthesized by fusion of carbon and hydrogen in supernovas. Due to the volatility of elemental nitrogen and its common compounds with hydrogen and oxygen, nitrogen is far less common on the rocky planets of the inner Solar System, and it is a relatively rare element on Earth as a whole. However, as on Earth, nitrogen and its compounds occur commonly as gases in the atmospheres of planets and moons that have atmospheres.

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Many industrially important compounds, such as ammonia, nitric acid, organic nitrates (propellants and explosives), and cyanides, contain nitrogen. The extremely strong bond in elemental nitrogen dominates nitrogen chemistry, causing difficulty for both organisms and industry in converting the N2 into useful compounds, but at the same time causing release of large amounts of often useful energy when the compounds burn, explode, or decay back into nitrogen gas. Synthetically-produced ammonia and nitrates are key industrial fertilizers and fertilizer nitrates are key pollutants in causing the eutrophication (overabundance of algae) of water systems.

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Nitrogen

Nitrogen occurs in all organisms, primarily in amino acids (and thus proteins) and also in the nucleic acids (DNA and RNA). The human body contains about 3% by weight of nitrogen, the fourth most abundant element in the body after oxygen, carbon, and hydrogen. The nitrogen cycle describes movement of the element from the air, into the biosphere and organic compounds, then back into the atmosphere. 

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NitrogenHistory and etymologyNitrogen is formally considered to have been discovered by Scottish physician Daniel Rutherford in 1772, who called it noxious air or fixed air. The fact that there was constituent of air that does not support combustion was clear to Rutherford. Nitrogen was also studied at about the same time by Carl Wilhelm Scheele, Henry Cavendish, and Joseph Priestley, who referred to it as burnt air or phlogisticated air. Nitrogen gas was inert enough that Antoine Lavoisier referred to it as "mephitic air" or azote, from the Greek word ἄζωτος (azotos) meaning "lifeless". In it, animals died and flames were extinguished. Lavoisier's name for nitrogen is used in many languages and still remains in English in the common names of many compounds, such as hydrazine and compounds of the azide ion.

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History and etymologyThe English word nitrogen (1794) entered the language from the French nitrogène, coined in 1790 by French chemist Jean-Antoine Chaptal (1756–1832), from the Greek "nitron" (sodium carbonate) and the French gène (producing). The gas had been found in nitric acid. Chaptal's meaning was that nitrogen gas is the essential part of nitric acid, in turn formed from saltpetre (potassium nitrate), then known as nitre. This word in the more ancient world originally described sodium salts that did not contain nitrate, and is a cognate of natron. 

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NitrogenBiological role Nitrogen is an essential building block of amino and nucleic acids, essential to life on Earth.Elemental nitrogen in the atmosphere cannot be used directly by either plants or animals, and must be converted to a reduced (or 'fixed') state to be useful for higher plants and animals. Precipitation often contains substantial quantities of ammonium and nitrate, thought to result from nitrogen fixation by lightning and other atmospheric electric phenomena. This was first proposed by Liebig in 1827 and later confirmed. However, because ammonium is preferentially retained by the forest canopy relative to atmospheric nitrate, most fixed nitrogen reaches the soil surface under trees as nitrate. Soil nitrate is preferentially assimilated by tree roots relative to soil ammonium.

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NitrogenBiological role Specific bacteria (e.g., Rhizobium trifolium) possess nitrogenase enzymes that can fix atmospheric nitrogen (see nitrogen fixation) into a form (ammonium ion) that is chemically useful to higher organisms. This process requires a large amount of energy and anoxic conditions. Such bacteria may live freely in soil but normally exist in a symbiotic relationship in the root nodules of leguminous plants (e.g. clover, or soybean). Nitrogen-fixing bacteria are also symbiotic with a number of unrelated plant species such as lichens. As part of the symbiotic relationship, the plant converts the 'fixed' ammonium ion to nitrogen oxides and amino acids to form proteins and other molecules, (e.g.,alkaloids). In return for the 'fixed' nitrogen, the plant secretes sugars to the symbiotic bacteria. Legumes maintain an anaerobic (oxygen free) environment for their nitrogen-fixing bacteria.

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NitrogenBiological role Plants are able to assimilate nitrogen directly in the form of nitrates that may be present in soil from natural mineral deposits, artificial fertilizers, animal waste, or organic decay (as the product of bacteria, but not bacteria specifically associated with the plant). Nitrates absorbed in this fashion are converted to nitrites by the enzyme nitrate reductase, and then converted to ammonia by another enzyme called nitrite reductase. Nitrogen compounds are basic building blocks in animal biology as well. Animals use nitrogen-containing amino acids from plant sources as starting materials for all nitrogen-compound animal biochemistry, including the manufacture of proteins and nucleic acids. Plant-feeding insects are dependent on nitrogen in their diet, such that varying the amount of nitrogen fertilizer applied to a plant can affect the reproduction rate of insects feeding on fertilized plants.

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PhosphateA phosphate is a salt of phosphoric acid. The phosphate ion has the empirical formula PO4. It consists of one central phosphorus atom surrounded by four oxygen atoms. Phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. The bonds in ADP and ATP contain high amounts of energy which give them their vital role in all living organisms. The addition and removal of phosphate from proteins in all cells is a pivotal strategy in the regulation of metabolic processes. Phosphate is useful in animal cells as a buffering agent. An important occurrence of phosphates in biological systems is as the structural material of bone and teeth. These structures are made of crystalline calcium phosphate in the form of hydroxyapatite. The hard dense enamel of mammalian teeth consists of fluoroapatite, an hydroxy calcium phosphate where some of the hydroxyl groups have been replaced by fluoride ions. 148

Potassium

Potassium is a chemical element with symbol K (from Neo-Latin kalium). Because potassium and sodium are chemically very similar, their salts were not at first differentiated. Potassium ions are necessary for the function of all living cells. Potassium ion diffusion is a key mechanism in nerve transmission, and potassium depletion in animals, including humans, results in various cardiac dysfunctions. Potassium accumulates in plant cells, and thus fresh fruits and vegetables are a good dietary source of it. Heavy crop production rapidly depletes soils of potassium, and agricultural fertilizers consume 95% of global potassium chemical production.

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History Kalium was taken from the word "alkali", which in turn came from Arabic: "plant ashes." The similar-sounding English term alkali is from this same root – potassium in Modern Standard Arabic is būtāsyūm.The English name for the element potassium comes from the word "potash", and refers to the method by which potash was obtained – leaching the ash of burnt wood or tree leaves and evaporating the solution in a pot.

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Potassium

Biological role The action of the sodium-potassium pump is an example of primary active transport. The two carrier proteins on the left are using ATP to move sodium out of the cell against the concentration gradient. The proteins on the right are using secondary active transport to move potassium into the cell.Potassium is the eighth or ninth most common element by mass (0.2%) in the human body, so that a 60 kg adult contains a total of about 120 g of potassium. The body has about as much potassium as sulfur and chlorine, and only the major minerals calcium and phosphorus are more abundant.

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Biological role Potassium cations are important in neuron (brain and nerve) function, and in influencing osmotic balance between cells and the interstitial fluid, with their distribution mediated in all animals by the Na+/K+-ATPase pump. This ion pump uses ATP to pump three sodium ions out of the cell and two potassium ions into the cell, thus creating an electrochemical gradient over the cell membrane. In addition, the highly selective potassium ion channels are crucial for the hyperpolarization, in for example neurons, after an action potential is fired.

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Membrane polarization Potassium is also important in preventing muscle contraction and the sending of all nerve impulses in animals through action potentials. A shortage of potassium in body fluids may cause a potentially fatal condition known as hypokalemia, typically resulting from vomiting, diarrhea, and/or increased diuresis. Deficiency symptoms include muscle weakness, paralytic ileus, ECG abnormalities, decreased reflex response and in severe cases respiratory paralysis, alkalosis and cardiac arrhythmia.

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Potassium

Filtration and excretion Potassium is an essential macromineral in human nutrition; it is the major cation (positive ion) inside animal cells, and it is thus important in maintaining fluid and electrolyte balance in the body. Sodium makes up most of the cations of blood plasma at a reference range of about 145 mmol/L (3.345 g)(1mmol/L = 1mEq/L), and potassium makes up most of the cell fluid cations at about 150 mmol/L (4.8 g). Plasma is filtered through the glomerulus of the kidneys in enormous amounts, about 180 liters per day. Thus 602 g of sodium and 33 g of potassium are filtered each day. All but the 1–10 g of sodium and the 1–4 g of potassium likely to be in the diet must be reabsorbed. Sodium must be reabsorbed in such a way as to keep the blood volume exactly right and the osmotic pressure correct; potassium must be reabsorbed in such a way as to keep serum concentration as close as possible to 4.8 mmol/L (about 0.190 g/L).

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Filtration and excretion Sodium pumps in the kidneys must always operate to conserve sodium. Potassium must sometimes be conserved also, but, as the amount of potassium in the blood plasma is very small and the pool of potassium in the cells is about thirty times as large, the situation is not so critical for potassium. Since potassium is moved passively[ in counter flow to sodium in response to an apparent (but not actual) Donnan equilibrium, the urine can never sink below the concentration of potassium in serum except sometimes by actively excreting water at the end of the processing. Potassium is secreted twice and reabsorbed three times before the urine reaches the collecting tubules. At that point, it usually has about the same potassium concentration as plasma. At the end of the processing, potassium is secreted one more time if the serum levels are too high. 

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Potassium

Filtration and excretion If potassium were removed from the diet, there would remain a minimum obligatory kidney excretion of about 200 mg per day when the serum declines to 3.0–3.5 mmol/L in about one week, and can never be cut off completely, resulting in hypokalemia and even death. The potassium moves passively through pores in the cell membrane. When ions move through pumps there is a gate in the pumps on either side of the cell membrane and only one gate can be open at once. As a result, approximately 100 ions are forced through per second. Pores have only one gate, and there only one kind of ion can stream through, at 10 million to 100 million ions per second. The pores require calcium in order to open although it is thought that the calcium works in reverse by blocking at least one of the pores.

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Potassium

In diet Adequate intake A potassium intake sufficient to support life can in general be guaranteed by eating a variety of foods. Clear cases of potassium deficiency (as defined by symptoms, signs and a below-normal blood level of the element) are rare in healthy individuals. Foods rich in potassium include parsley, dried apricots, dried milk,chocolate, various nuts (especially almonds and pistachios), potatoes, bamboo shoots, bananas, avocados, soybeans, and bran, although it is also present in sufficient quantities in most fruits, vegetables, meat and fish.

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In diet Optimal intake Epidemiological studies and studies in animals subject to hypertension indicate that diets high in potassium can reduce the risk of hypertension and possibly stroke (by a mechanism independent of blood pressure), and a potassium deficiency combined with an inadequate thiamine intake has produced heart disease in rats. There is some debate regarding the optimal amount of dietary potassium. For example, the 2004 guidelines of the Institute of Medicine specify a DRI of 4,000 mg of potassium (100 mEq), though most Americans consume only half that amount per day, which would make them formally deficient as regards this particular recommendation.

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Potassium

Medical supplementation and disease Supplements of potassium in medicine are most widely used in conjunction with loop diuretics and thiazides, classes of diuretics that rid the body of sodium and water, but have the side-effect of also causing potassium loss in urine. A variety of medical and non-medical supplements are available. Potassium salts such as potassium chloride may be dissolved in water, but the salty/bitter taste of high concentrations of potassium ion make palatable high concentration liquid supplements difficult to formulate. Typical medical supplemental doses range from 10 mmol (400 mg, about equal to a cup of milk or 6 fl oz of orange juice) to 20 mmol (800 mg) per dose.

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Potassium

Medical supplementation and disease Potassium salts are also available in tablets or capsules, which for therapeutic purposes are formulated to allow potassium to leach slowly out of a matrix, as very high concentrations of potassium ion (which might occur next to a solid tablet of potassium chloride) can kill tissue, and cause injury to the gastric or intestinal mucosa. For this reason, non-prescription supplement potassium pills are limited by law in the US to only 99 mg of potassium.Individuals suffering from kidney diseases may suffer adverse health effects from consuming large quantities of dietary potassium. End stage renal failure patients undergoing therapy by renal dialysis must observe strict dietary limits on potassium intake, as the kidneys control potassium excretion, and buildup of blood concentrations of potassium (hyperkalemia) may trigger fatal cardiac arrhythmia.

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Sodium

Sodium is a chemical element with the symbol Na (from Latin: natrium). Sodium is the sixth most abundant element in the Earth's crust. Chloride and sodium are the most common dissolved elements by weight in the Earth's bodies of oceanic water. In animals, sodium ions are used against potassium ions to build up charges on cell membranes, allowing transmission of nerve impulses when the charge is dissipated. The consequent need of animals for sodium causes it to be classified as a dietary inorganic macro-mineral. 

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Sodium

History Salt has been an important commodity in human activities, as shown by the English word salary, which derives from salarium, the wafers of salt sometimes given to Roman soldiers along with their other wages. In medieval Europe, a compound of sodium with the Latin name of sodanum was used as a headache remedy. The name sodium is thought to originate from the Arabic suda, meaning headache. The chemical abbreviation for sodium was first published by Jöns Jakob Berzelius in his system of atomic symbols, and is a contraction of the element's new Latin name natrium, which refers to the Egyptian natron, a natural mineral salt.  

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Sodium

Biological role In humans, sodium is an essential nutrient that regulates blood volume, blood pressure, osmotic equilibrium and pH; the minimum physiological requirement for sodium is 500 milligrams per day. Sodium chloride is the principal source of sodium in the diet, and is used as seasoning and preservative, such as for pickling and jerky; most of it comes from processed foods. The DRI for sodium is 2.3 grams per day, but on average people in the United States consume 3.4 grams per day, the minimum amount that promotes hypertension; this in turn causes 7.6 million premature deaths worldwide.  

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Sodium

Biological role The renin-angiotensin system regulates the amount of fluids and sodium in the body. Reduction of blood pressure and sodium concentration in the kidney result in the production of renin, which in turn produces aldosterone and angiotensin, retaining sodium in the urine. Because of the increase in sodium concentration, the production of renin decreases, and the sodium concentration returns to normal. Sodium is also important in neuron function and osmoregulation between cells and the extracellular fluid, their distribution mediated in all animals by Na+/K+-ATPase; hence, sodium is the most prominent cation in extracellular fluid.

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Urea

Urea is an organic compound with the chemical formula CO(NH2)2. Urea serves an important role in the metabolism of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the urine of mammals. It is a colorless, odorless solid, highly soluble in water and practically non-toxic. Dissolved in water, it is neither acidic nor alkaline. The body uses it in many processes, the most notable one being nitrogen excretion. Urea is widely used in fertilizers as a convenient source of nitrogen. Urea is also an important raw material for the chemical industry. The discovery by Friedrich Wöhler in 1828 that urea can be produced from inorganic starting materials was an important conceptual milestone in chemistry, as it showed for the first time that a substance previously known only as a byproduct of life could be synthesized in the lab without any biological starting materials, contradicting the widely held doctrine of vitalism.

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Urea

HistoryUrea was first discovered in urine in 1727 by the Dutch scientist Herman Boerhaave, though this discovery is often attributed to the French chemist Hilaire Rouelle. In 1828, the German chemist Friedrich Wöhler obtained urea by treating silver cyanate with ammonium chloride. For this discovery, Wöhler is considered by many to be the father of organic chemistry. AgNCO + NH4Cl → (NH2)2CO + AgCl

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Urea

Physiology

Urea is synthesized in the body of many organisms as part of the urea cycle, either from the oxidation of amino acids or from ammonia. In this cycle, amino groups (NH2) donated by ammonia and aspartate are converted to urea. Urea production occurs in the liver. Urea is found dissolved in blood (in the reference range of 2.5 to 6.7 mmol/liter) and is excreted by the kidney as a component of urine. In addition, a small amount of urea is excreted in sweat.

Amino acids from ingested food that are not used for the synthesis of proteins and other biological substances are oxidized by the body, yielding urea and carbon dioxide, as an alternative source of energy.The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle.

Ammonia (NH3) is another common byproduct of the metabolism of nitrogenous compounds. If allowed to accumulate, ammonia would raise the pH in cells to toxic levels. Therefore many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen. In water, the amine groups undergo slow displacement by water molecules, producing ammonia and carbonate anion. For this reason, old, stale urine has a stronger odor than fresh urine.

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UreaIn humans The handling of urea by the kidneys is a vital part of human metabolism. Besides its role as carrier of waste nitrogen, urea also plays a role in the countercurrent exchange system of the nephrons, in that it allows for re-absorption of water and critical ions from the excreted urine. Urea is reabsorbed in the nephrons, thus raising the osmolarity in the thin ascending limb of the loop of Henle, which in turn causes water to be reabsorbed. By action of the urea transporter 2, some of this reabsorbed urea will eventually flow back into the thin ascending limb of the tubule, through the collecting ducts, and into the excreted urine. This mechanism, which is controlled by the antidiuretic hormone, allows the body to create hyperosmotic urine, which has a higher concentration of dissolved substances than the blood plasma. This mechanism is important to prevent the loss of water, to maintain blood pressure, and to maintain a suitable concentration of sodium ions in the blood plasmas. 168

Urea

In humans The equivalent nitrogen content (in gram) of urea (in mmol) can be estimated by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to 6.25 grams of protein, and 1 gram of protein is roughly equivalent to 5 grams of muscle tissue. In situations such as muscle wasting, 1 mmol of excessive urea in the urine (as measured by urine volume in liters multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67 gram.

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Urea

In other species In aquatic organisms the most common form of nitrogen waste is ammonia, whereas land-dwelling organisms convert the toxic ammonia to either urea or uric acid. Urea is found in the urine of mammals and amphibians, as well as some fish. Birds and saurian reptiles have a different form of nitrogen metabolism, which requires less water and leads to nitrogen excretion in the form of uric acid.

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Agriculture Uses More than 90% of world production of urea is destined for use as a nitrogen-release fertilizer. Urea has the highest nitrogen content of all solid nitrogenous fertilizers in common use. Therefore, it has the lowest transportation costs per unit of nitrogen nutrient. The standard crop-nutrient rating of urea is 46-0-0. Many soil bacteria possess the enzyme urease, which catalyzes the conversion of the urea molecule to two ammonia molecules and one carbon dioxide molecule, thus urea fertilizers are very rapidly transformed to the ammonium form in soils. Excess nitrogen that runs from soils into water is a major cause of water pollution from agriculture. Ammonia and nitrate are readily absorbed by plants, and are the dominant sources of nitrogen for plant growth. Urea is also used in many multi-component solid fertilizer formulations. Urea is highly soluble in water and is, therefore, also very suitable for use in fertilizer solutions.

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Uric Acid

Uric acid has the formula C5H4N4O3. Uric acid is a product of the metabolic breakdown of purine nucleotides (found in high quantities in red meat, red wine, aged cheese). High blood concentrations of uric acid can lead to gout, diabetes and kidney stones.

 

Chemistry 

Uric acid was first isolated from kidney stones in 1776 by Scheele.Generally, the water solubility of uric acid is rather low. It has greater solubility in hot water than cold, allowing for easy recrystallization. This low solubility is significant for the etiology of gout. Uric acid precipitates in cooler areas of the body. Therefore, uric acid crystals may form in the 1st metatarsal phalangeal joint, causing the symptoms of gout.

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Uric Acid

Biology The enzyme xanthine oxidase makes uric acid from xanthine and hypoxanthine, which in turn are produced from other purines. In humans and higher primates, uric acid is the final oxidation (breakdown) product of purine metabolism and is excreted in urine. Both uric acid and ascorbic acid are strong reducing agents (electron donors) and potent antioxidants. In humans, over half the antioxidant capacity of blood plasma comes from uric acid.The Dalmatian dog has a genetic defect in uric acid uptake by the liver and kidneys, so this breed excretes uric acid directly into the urine.In humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5-25% of humans, impaired renal (kidney) excretion leads to hyperuricemia.

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Uric Acid

Genetics A proportion of people have mutations in the proteins responsible for the excretion of uric acid by the kidneys. This is what causes them to have the error in purine metabolism, causing gout. Medicine Uric acid concentrations in blood plasma above and below the normal range are known, respectively, as hyperuricemia and hypouricemia. Similarly, uric acid concentrations in urine above and below normal are known as hyperuricosuria and hypouricosuria. Such abnormal concentrations of uric acid are not medical conditions, but are associated with a variety of medical conditions.

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High uric acid High levels of uric acid is called hyperuricemia. Causes of high uric acidIn many instances, people have elevated uric acid levels for hereditary reasons.Diet may be a factor. High intake of dietary purine, high fructose corn syrup, and table sugar can cause increased levels of uric acid.Serum uric acid can be elevated due to reduced excretion by the kidneys. Fasting or rapid weight loss can temporarily elevate uric acid levels.Certain drugs, such as thiazide diuretics, can increase uric acid levels in the blood by interfering with renal clearance.

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Uric Acid

Gout Excess serum accumulation of uric acid in the blood can lead to a type of arthritis known as gout. This painful condition is the result of needle-like crystals of uric acid precipitating in joints, capillaries, skin, and other tissues. Kidney stones can also form through the process of formation and deposition of sodium urate microcrystals. A study found that men who drank two or more sugar-sweetened beverages a day have an 85% higher chance of developing gout than those who drank such beverages infrequently. Inflammation during attacks is commonly treated with NSAIDs or corticosteroids, and urate levels are managed with allopurinol, which inhibits xanthine oxidase and thus inhibits uric acid synthesis.

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Uric Acid

Lesch-Nyhan syndrome Lesch-Nyhan syndrome, an extremely rare inherited disorder, is also associated with very high serum uric acid levels. Spasticity, involuntary movement and cognitive retardation as well as manifestations of gout are seen in cases of this syndrome.

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Uric Acid

Cardiovascular disease Although uric acid can act as an antioxidant, excess serum accumulation is often associated with cardiovascular disease. It is not known whether this is causative (e.g., by acting as a prooxidant ) or a protective reaction taking advantage of urate's antioxidant properties. The same may account for the putative role of uric acid in the etiology of stroke.

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Uric Acid

Type 2 diabetes The association of high serum uric acid with insulin resistance has been known since the early part of the 20th century, nevertheless, recognition of high serum uric acid as a risk factor for diabetes has been a matter of debate. In fact, hyperuricemia has always been presumed to be a consequence of insulin resistance rather than its precursor. However, a prospective follow-up study showed high serum uric acid is associated with higher risk of type 2 diabetes, independent ofobesity, dyslipidemia, and hypertension.

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Uric Acid

Metabolic syndrome Hyperuricemia is associated with components of metabolic syndrome. A study has suggested fructose-induced hyperuricemia may play a pathogenic role in the metabolic syndrome. This is consistent with the increased consumption in recent decades of fructose-containing beverages (such as fruit juices and soft drinks sweetened with sugar and high-fructose corn syrup) and the epidemic of diabetes and obesity.

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Uric Acid

Uric acid stone formation Saturation levels of uric acid in blood may result in one form of kidney stones when the urate crystallizes in the kidney. These uric acid stones are radiolucent and so do not appear on an abdominal plain X-ray, and thus their presence must be diagnosed by ultrasound for this reason. Very large stones may be detected on X-ray by their displacement of the surrounding kidney tissues. 

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Uric Acid

Uric acid stone formation

Uric acid stones, which form in the absence of secondary causes such as chronic diarrhea, vigorous exercise, dehydration, and animal protein loading, are felt to be secondary to obesity and insulin resistance seen in metabolic syndrome. Increased dietary acid leads to increased endogenous acid production in the liver and muscles, which in turn leads to an increased acid load to the kidneys. This load is handled more poorly because of renal fat infiltration and insulin resistance, which are felt to impair ammonia excretion (a buffer). The urine is therefore quite acidic, and uric acid becomes insoluble, crystallizes and stones form. In addition, naturally present promoter and inhibitor factors may be affected. This explains the high prevalence of uric stones and unusually acidic urine seen in patients with type 2 diabetes. Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals" (heterogeneous nucleation).

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Uric AcidLow uric acid (hypouricemia)

Causes of low uric acid Low dietary zinc intakes cause lower uric acid levels. This effect can be even more pronounced in women taking oral contraceptive medication.Xanthine oxidase is an Fe (iron) enzyme, so people with Fe deficiency (the most common cause of anemia in young women) can experience hypouricemia.Xanthine oxidase loses its function and gains ascorbase function when some of the Fe atoms in XO are replaced with Cu atoms. Accordingly, people with high Cu/Fe can experience hypouricemia and vitamin C deficiency, resulting in oxidative damage. Since estrogen increases the half-life of Cu, women with very high estrogen levels and intense blood loss during menstruation are likely to have a high Cu/Fe and present with hypouricemia.

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Uric Acid

Sevelamer, a drug indicated for prevention of hyperphosphataemia in patients with chronic renal failure, can significantly reduce serum uric acid.

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Uric Acid

Multiple sclerosis Lower serum values of uric acid have been associated with multiple sclerosis (MS). A 2006 study found elevation of serum uric acid values in multiple sclerosis patients, by oral supplementation with inosine, resulted in lower relapse rates, and no adverse effects.  Normalizing low uric acid Correcting low or deficient zinc levels can help elevate serum uric acid. Inosine can be used to elevate uric acid levels. Zn inhibits Cu absorption, helping to reduce the high Cu/Fe in some people with hypouricemia. Fe supplements can ensure adequate Fe reserves (ferritin above 25 ng/dl), also correcting the high Cu/Fe.

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Uric Acid

Oxidative stress Uric acid may be a marker of oxidative stress, and may have a potential therapeutic role as an antioxidant. On the other hand, like other strong reducing substances such as ascorbate, uric acid can also act as a prooxidant. Thus, it is unclear whether elevated levels of uric acid in diseases associated with oxidative stress such as stroke and atherosclerosis are a protective response or a primary cause. For example, some researchers propose hyperuricemia-induced oxidative stress is a cause of metabolic syndrome. On the other hand, plasma uric acid levels correlate with longevity in primates and other mammals. This is presumably a function of urate's antioxidant properties.

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Uric Acid

Sources

Purines are found in high amounts in animal food products, such as liver and sardines. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.

Examples of high purine and Fe sources include: sweetbreads, anchovies, sardines, liver, beef kidneys, brains, herring, mackerel, scallops, game meats, and gravy.

One serving of meat or seafood (3 oz = 85 g) mildly increases risk of gout, while two servings increase risk by at least 40%. Milk products reduce the risk of gout notably, whereas total protein intake has no effect.

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Urea Cycle

The urea cycle is a series of biochemical reactions occurring in many animals that produces urea from ammonia(NH3). In mammals, the urea cycle takes place primarily in the liver, and to a lesser extent in the kidney.

Function Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like urea or uric acid, which are much less toxic. Insufficiency of the urea cycle occurs in some genetic disorders (inborn errors of metabolism), and in liver failure. The result of liver failure is accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic encephalopathy.

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Urea Cycle

Reactions The urea cycle consists of five reactions: two are in the mitochondria and three are in the cytoplasm. The cycle converts two amino groups, one from NH4+ and one from Aspartate (an amino acid), and a carbon atom from HCO3−, to the relatively nontoxic excretion product urea at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP). Ornithine is the carrier of these carbon and nitrogen atoms.

The overall formula for the urea cycle is this:2 NH3 + CO2 + 3 ATP + H2O → urea + 2 ADP + 4 Pi + AMP

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Urea Cycle

This process requires energy, but it is necessary to convert the toxic ammonia into non-toxic urea to transport it to the kidneys to remove the nitrogen waste.

Note that reactions related to the urea cycle also cause the production of 2 NADH, so the urea cycle releases slightly more energy than it consumes.

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Urea Cycle

Inherited deficiencies in the cycle enzymes do not result in a decrease in urea.

Rather, the deficient enzyme's substrate builds up all the way back up the cycle to NH4+, resulting in hyperammonemia (elevated [NH4+]).

A high [NH4+] puts an enormous strain on the NH4+-clearing system, especially in the brain (symptoms of urea cycle enzyme deficiencies include mental retardation and lethargy).

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