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How do kidney cells excrete their own wastes?

How do kidney cells excrete their own wastes?


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The kidney is composed of tissues, and those tissues are made up of numerous cells - so how do these cells excrete their wastes?

Lastly, are there any wastes in the venous blood (renal vein), what makes the renal artery and vein different? - what substances do they each carry?


I checked my anatomy notes and online figures about the kidney. There is no mention about dedicated arteries for feeding kidney cells. So it does not work the same way as the heart does, where there is a dedicated coronary artery. The kidneys use the same blood vessels for filtering and for nutrition/waste transport purposes too.

  • Figure 1 - kidney anatomy - source

  • Figure 2 - nephron anatomy - source

The urea is created from NH4+ and HCO3- in the liver (mostly) and the kidney because of blood pH regulation purposes. It neutralizes the HCO3- created by the lungs from CO2 and OH-.

The urea cycle (also known as the Ornithine cycle) is a cycle of biochemical reactions occurring in many animals that produces urea ((NH2)2CO) from ammonia (NH3). This cycle was the first metabolic cycle discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. In mammals, the urea cycle takes place primarily in the liver, and to a lesser extent in the kidney.

In chemical terms, urea synthesis is an irreversible, energy driven neutralization of the strong base HCO3- by the weak acid NH4+, and the average daily excretion of 30 g of urea is equivalent to the disposal of about 1 mol of HCO3- per day. Thus, a major function of hepatic urea synthesis is to effect this neutralization, without which the body would otherwise be confronted by a major load of alkali.

Urea is excreted by the kidney, and is normally present in plasma and body fluids at a concentration of 3.0-6.5 mmol/L.

  • wikipedia - Ornithine cycle
  • Textbook of Hepatology - Ammonia, urea production and pH regulation - Dieter Häussinger
  • 1984 - The role of ureagenesis in pH homeostasis

The kidney reabsorbs urea in order to concentrate the urine:

  • Figure 3 - nephron with material transports - urea resorption at the end of the urine creation process - source

About 40% of the urea filtered is normally found in the final urine, since there is more reabsorption than secretion along the nephron.

  • wikipedia - Renal urea handling:

  • 2007 - Critical Role of Urea in the Urine-Concentrating Mechanism

The kidney secretes the urea to the urine, but it absorbs more by the reabsorption than it secreted.

The kidney freely filters urea at the glomerulus, and then it both reabsorbs and secretes it. Because the tubules reabsorb more urea than they secrete, the amount of urea excreted in the urine is less than the quantity filtered. In the example shown in Figure 36-1A (i.e., average urine flow), the kidneys excrete ∼40% of the filtered urea. The primary sites for urea reabsorption are the proximal tubule and the medullary collecting duct, whereas the primary sites for secretion are the thin limbs of the loop of Henle.

So if we are talking about urea, then it is secreted to the urine. If we are talking about other waste products, then e.g. CO2 is certainly handled by the veins.


The kidneys keep the composition, or makeup, of the blood stable, which lets the body function.

Each kidney is made up of about a million filtering units called nephrons. The nephron includes a filter, called the glomerulus, and a tubule.

The nephrons work through a two-step process. The glomerulus lets fluid and waste products pass through it; however, it prevents blood cells and large molecules, mostly proteins, from passing. The filtered fluid then passes through the tubule, which sends needed minerals back to the bloodstream and removes wastes.


This is how an organism gets rid of waste products.

Every living thing makes waste, or material the body no longer needs or cannot use. As our bodies use the oxygen we inhale, for example, we produce waste carbon dioxide. When we breathe out that carbon dioxide, we are excreting it. We also produce waste from food particles we can’t digest. Our bodies excrete this solid waste as poop, and liquid waste as pee. We can even excrete waste products through the skin in our sweat.

Waste products can harm organisms if they aren’t excreted. If we did not get rid of extra carbon dioxide, for example, we would get tired and confused. We can even faint or die. Animals have different body systems that separate waste. Human excretions, as well as those from other animals, usually leave the body after passing through the lungs, kidneys and skin. But single-celled organisms such as bacteria produce waste, too. They excrete their chemical waste through the membrane that separates them from their environment.

One organism’s trash is another one’s treasure, though. Bacteria live on our skin, and eagerly dine on our sweat. Plants excrete oxygen as their waste product — and we can’t live without it.

In a sentence

As if they weren’t bad enough, bed bugs excrete a chemical in their poop that can make people itch.

Power Words

bacteria: (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals). Bacteria are one of the three domains of life on Earth.

bed bug: A parasitic insect that feeds exclusively on blood. The common bed bug, Cimex lectularius , sucks human blood and is mainly active at night. The insect’s bite can cause skin rashes and welts that look like a mosquito bite.

bug: The slang term for an insect. Sometimes it’s even used to refer to a germ. (in computing) Slang term for a glitch in computer code, the instructions that direct the operations of a computer.

carbon: The chemical element having the atomic number 6. It is the physical basis of all life on Earth. Carbon exists freely as graphite and diamond. It is an important part of coal, limestone and petroleum, and is capable of self-bonding, chemically, to form an enormous number of chemically, biologically and commercially important molecules. (in climate studies) The term carbon sometimes will be used almost interchangeably with carbon dioxide to connote the potential impacts that some action, product, policy or process may have on long-term atmospheric warming.

carbon dioxide: (or CO2) A colorless, odorless gas produced by all animals when the oxygen they inhale reacts with the carbon-rich foods that they’ve eaten. Carbon dioxide also is released when organic matter burns (including fossil fuels like oil or gas). Carbon dioxide acts as a greenhouse gas, trapping heat in Earth’s atmosphere. Plants convert carbon dioxide into oxygen during photosynthesis, the process they use to make their own food.

chemical: A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.

digest: (noun: digestion) To break down food into simple compounds that the body can absorb and use for growth. Some sewage-treatment plants harness microbes to digest — or degrade — wastes so that the breakdown products can be recycled for use elsewhere in the environment.

environment: The sum of all of the things that exist around some organism or the process and the condition those things create. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature and humidity (or even the placement of things in the vicinity of an item of interest).

excrete: To remove waste products from the body, such as in the urine.

excretion: The process of removing waste products, which are produced by every living organism.

itch: A sensation on the skin that causes a person or animal to want to scratch. Itch sensations can be short-lived, such as when they are caused by a mosquito bite, or they can be chronic, even lasting for years without relief.

kidney: Each in a pair of organs in mammals that filters blood and produces urine.

membrane: A barrier which blocks the passage (or flow through) of some materials depending on their size or other features. Membranes are an integral part of filtration systems. Many serve that same function as the outer covering of cells or organs of a body.

organism: Any living thing, from elephants and plants to bacteria and other types of single-celled life.

oxygen: A gas that makes up about 21 percent of Earth's atmosphere. All animals and many microorganisms need oxygen to fuel their growth (and metabolism).

particle: A minute amount of something.

waste: Any materials that are left over from biological or other systems that have no value, so they can be disposed of as trash or recycled for some new use.

About Bethany Brookshire

Bethany Brookshire was a longtime staff writer at Science News for Students. She has a Ph.D. in physiology and pharmacology and likes to write about neuroscience, biology, climate and more. She thinks Porgs are an invasive species.

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Excretion

Ectotherms: depend on external environment for temperature regulation.

Endotherms: generate their own heat from metabolic reactions.

  1. Epidermis: Surface layer composed of dead cells with a melanin pigment.
  2. Dermis tissue: Connective tissue to contain and support skin structures e.g. sweat glands, nerve and thermal receptors.

Epidermis: protects from UV rays (due to melanin pigment) and general barrier to pathogens.

Sebum oil: acts as a surface disinfectant.

  1. Makes Vitamin D
  2. Energy Storage in fat tissue
  3. Excretion by sweating
  4. Temperature regulation:
  • Hair stands on skin due to erector muscle contraction- Piloerection. Holds warm air around skin.
  • Blood vessel contraction- Vasoconstriction.
  • Shivering.
  • Hair lies flat.
  • Sweating.
  • Blood vessels come close to surface. This causes blushing.

Organs of Excretion:

Waste Products:

The excretory system:

The kidneys:

  • Excretion
  • Osmoregulation (water and salt regulation)
  • pH control

Urine Production in the Nephron: (This is a basic analysis of the nephron system)

  1. Blood enters the afferent arteriole into the glomerulus.
  2. Filtration due to blood pressure forces water and waste products out of blood. Filtration occurs in the Cortex of Kidney.
  3. Useful substances are reabsorbed and waste is transported through Bowman’s capsule.
  4. Most water in filtrate is diffused out of convoluted tubule into capillaries. Glucose and other minerals are absorbed by active transport.
  5. The ascending limb of the loop of Henle absorbs most salt. Reabsorption of materials occurs in the Medulla and the Cortex.
  6. The distal convoluted tubule adjusts the filtrate’s pH level before it is expelled into the collecting duct.

Kidney control of urea concentration:

  • If salt level are too high or cells are dehydrated the hormone ADH (Anti-diuretic hormone) triggers more absorption of water in the distal convoluted tubule and collecting ducts. This increases urea concentration in urine but the overall urine concentration is reduced.
  • If low salt levels exist then no ADH is made and volume of urine remains constant or increased.

The Bladder:

Urine is the carried from both kidneys by the ureters to the bladder.

Function: It is used in the storage of urine from the Kidneys. Urine is then transported from the bladder by a tube called the urethra.


Tuesday, September 22, 2015

The energy required for maintenance and proper functioning of the human body is supplied by food. After it is broken into fragments by chewing (see Teeth) and mixed with saliva, digestion begins. The food passes down the gullet into the stomach, where the process is continued by the gastric and intestinal juices. Thereafter, the mixture of food and secretions, called chyme, is pushed down the alimentary canal by peristalsis, rhythmic contractions of the smooth muscle of the gastrointestinal system.

The contractions are initiated by the parasympathetic nervous system such muscular activity can be inhibited by the sympathetic nervous system. Absorption of nutrients from chyme occurs mainly in the small intestine unabsorbed food and secretions and waste substances from the liver pass to the large intestines and are expelled as feces. Water and water-soluble substances travel via the bloodstream from the intestines to the kidneys, which absorb all the constituents of the blood plasma except its proteins. The kidneys return most of the water and salts to the body, while excreting other salts and waste products, along with excess water, as urine.

A primary function of kidneys is the removal of poisonous wastes from the blood. Chief among these wastes are the nitrogen-containing compounds urea and uric acid, which result from the breakdown of proteins and nucleic acids. Life-threatening illnesses occur when too many of these waste products accumulate in the bloodstream. Fortunately, a healthy kidney can easily rid the body of these substances.


Excretion

Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. [1] This is in contrast with secretion, where the substance may have specific tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in mammals, urine is expelled through the urethra, which is part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell.

During life activities such as cellular respiration, several chemical reactions take place in the body. These are known as metabolism. These chemical reactions produce waste products such as carbon dioxide, water, salts, urea and uric acid. Accumulation of these wastes beyond a level inside the body is harmful to the body. The excretory organs remove these wastes. This process of removal of metabolic waste from the body is known as excretion.

Green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis. Oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of excess water by transpiration and guttation. It has been shown that the leaf acts as an 'excretophore' and, in addition to being a primary organ of photosynthesis, is also used as a method of excreting toxic wastes via diffusion. Other waste materials that are exuded by some plants — resin, saps, latex, etc. are forced from the interior of the plant by hydrostatic pressures inside the plant and by absorptive forces of plant cells. These latter processes do not need added energy, they act passively. However, during the pre-abscission phase, the metabolic levels of a leaf are high. [2] [3] Plants also excrete some waste substances into the soil around them. [4]

In animals, the main excretory products are carbon dioxide, ammonia (in ammoniotelics), urea (in ureotelics), uric acid (in uricotelics), guanine (in Arachnida), and creatine. The liver and kidneys clear many substances from the blood (for example, in renal excretion), and the cleared substances are then excreted from the body in the urine and feces. [5]

Aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other nitrogenous materials, i.e. urea, that are less harmful as there is less water in the environment and ammonia itself is toxic. This process is called detoxication. [6]

Birds excrete their nitrogenous wastes as uric acid in the form of a paste. Although this process is metabolically more expensive, it allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, the saline solution leaving through nostrils in the beak.

In insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines. The metabolic waste is then released from the body along with fecal matter.

The excreted material may be called ejecta. [7] In pathology the word ejecta is more commonly used. [8]


Contents

Urinary system

The kidneys are large, bean-shaped organs which are present on each side of the vertebral column in the abdominal cavity. Humans have two kidneys and each kidney is supplied with blood from the renal artery. The kidneys remove from the blood the nitrogenous wastes such as urea, as well as salts and excess water, and excrete them in the form of urine. This is done with the help of millions of nephrons present in the kidney. The filtrated blood is carried away from the kidneys by the renal vein (or kidney vein). The urine from the kidney is collected by the ureter (or excretory tubes), one from each kidney, and is passed to the urinary bladder. The urinary bladder collects and stores the urine until urination. The urine collected in the bladder is passed into the external environment from the body through an opening called the urethra.

Kidneys

The kidney's primary function is the elimination of waste from the bloodstream by production of urine. They perform several homeostatic functions such as:-

  1. Maintain volume of extracellular fluid
  2. Maintain ionic balance in extracellular fluid
  3. Maintain pH and osmotic concentration of the extracellular fluid.
  4. Excrete toxic metabolic by-products such as urea, ammonia, and uric acid.

The way the kidneys do this is with nephrons. There are over 1 million nephrons in each kidney these nephrons act as filters inside the kidneys. The kidneys filter needed materials and waste, the needed materials go back into the bloodstream, and unneeded materials become urine and are gotten rid of.

In some cases, excess wastes crystallize as kidney stones. They grow and can become painful irritants that may require surgery or ultrasound treatments. Some stones are small enough to be forced into the urethra.

Ureter

The ureters are muscular ducts that propel urine from the kidneys to the urinary bladder. In the human adult, the ureters are usually 25–30 cm (10–12 in) long. In humans, the ureters arise from the renal pelvis on the medial aspect of each kidney before descending towards the bladder on the front of the psoas major muscle. The ureters cross the pelvic brim near the bifurcation of the iliac arteries (which they run over). This "pelviureteric junction" is a common site for the impaction of kidney stones (the other being the uteterovesical valve). The ureters run posteriorly on the lateral walls of the pelvis. They then curve anteriormedially to enter the bladder through the back, at the vesicoureteric junction, running within the wall of the bladder for a few centimeters. The backflow of urine is prevented by valves known as ureterovesical valves. In the female, the ureters pass through the mesometrium on the way to the bladder.

Urinary bladder

The urinary bladder is the organ that collects waste excreted by the kidneys prior to disposal by urination. It is a hollow muscular, and distensible (or elastic) organ, and sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra.

Embryologically, the bladder is derived from the urogenital sinus, and it is initially continuous with the allantois. In human males, the base of the bladder lies between the rectum and the pubic symphysis. It is superior to the prostate, and separated from the rectum by the rectovesical excavation. In females, the bladder sits inferior to the uterus and anterior to the vagina. It is separated from the uterus by the vesicouterine excavation. In infants and young children, the urinary bladder is in the abdomen even when empty.

Urethra

In anatomy, the (from Greek – ourethra) is a tube which connects the urinary bladder to the outside of the body. In humans, the urethra has an excretory function in both genders to pass.

Respiratory system

One of the main functions of the lungs is to diffuse gaseous wastes, such as carbon dioxide, from the bloodstream as a normal part of respiration.

Gastrointestinal tract

The large intestine's main function is to transport food particles through the body and expel the indigestible parts at the other end, but it also collects waste from throughout the body. The typical brown colour of mammal waste is due to bilirubin, a breakdown product of normal heme catabolism. [1] The lower part of the large intestine also extracts any remaining usable water and then removes solid waste. At about 10 feet long in humans, it transports the wastes through the tubes to be excreted.

Biliary system

The liver detoxifies and breaks down chemicals, poisons and other toxins that enter the body. For example, the liver transforms ammonia (which is poisonous) into urea in fish, amphibians and mammals, and into uric acid in birds and reptiles. Urea is filtered by the kidney into urine or through the gills in fish and tadpoles. Uric acid is paste-like and expelled as a semi-solid waste (the "white" in bird excrements). The liver also produces bile, and the body uses bile to break down fats into usable fats and unusable waste.

Invertebrates lack a liver, but most terrestrial groups, like insects, possesses a number of blind guts that serve the similar functions. Marine invertebrates do not need the ammonia conversion of the liver, as they can usually expel ammonia directly by diffusion through the skin.

Integumentary system

Sweat glands in the skin secrete a fluid waste called sweat or perspiration however, its primary functions are temperature control and pheromone release. Therefore, its role as a part of the excretory system is minimal. Sweating also maintains the level of salt in the body.

In mammals, the skin excretes sweat through sweat glands throughout the body. The sweat, helped by salt, evaporates and helps to keep the body cool when it is warm. In amphibians, the lungs are very simple, and they lack the necessary means to the exhale like other tetrapods can. The moist, scale-less skin is therefore essential in helping to rid the blood of carbon dioxide, and also allows for urea to be expelled through diffusion when submerged. [2]

In small-bodied marine invertebrates, the skin is the most important excretory organ. That is particularly true for acoelomate groups like cnidarians, flatworms and nemerteans, who have no body cavities and hence no body fluid that can be drained or purified by nephrons, which is the reason acoelomate animals are thread-like (nemertans), flat (flatworms) or only consist of a thin layer of cells around a gelatinous non-cellular interior (cnidarians). [3]

Eccrine

Like sweat glands, eccrine glands allow excess water to leave the body. The majority of eccrine glands are located mainly on the forehead, the bottoms of the feet, and the palms, although the glands are everywhere throughout the body. They help the body to maintain temperature control. Eccrine glands in the skin are unique to mammals. [ citation needed ]

Secretions of sweat from the eccrine glands play a large role in controlling the body temperature of humans. Regulation of body temperature, also known as thermoregulation, is very important when it comes to instances that bring the body's temperature outside of the homeostatic temperature such as with a fever or even exercise. [4] Together these glands make up the size of about one kidney and in one day a human can perspire amounts as much as 10 liters. The two functions consist of secretion of a filtrate in response to acetylcholine and reabsorption of sodium near the duct when there is water in excess so that a sweat can be surfacing the skin. [5]

There are three parts to the eccrine sweat gland and these are the pore, the duct, and the gland. The pore is the portion that goes through the outermost layer of the skin and is typically 5-10 microns in diameter. The duct is the part of the sweat gland that connects dermis cells to the epidermis. It is composed by two layers of cells and is between 10 and 20 microns in diameter. The gland does the actual secretion and it lies deep within the dermis. The cells that make up the gland are larger in size than the duct cells and its lumen is around 20 microns in diameter. [6]

After bile is produced in the liver, it is stored in the gall bladder. It is then secreted within the small intestine where it helps to emulsify fats in the same manner as a soap. Bile also contains bilirubin, which is a waste product.

Bile salts can be considered waste that is useful for the body given that they have a role in fat absorption from the stomach. They are excreted from the liver and along with blood flow they help to form the shape of the liver where they are excreted. For instance, if biliary drainage is impaired than that part of the liver will end up wasting away.

Biliary obstruction is typically due to masses blocking the ducts of the system such as tumors. The consequences of this depend on the site of blockage and how long it goes on for. There is inflammation of the ducts due to the irritation from the bile acids and this can cause infections. If rupture of the duct takes place it is very traumatic and even fatal. [7]

Urine

Within the kidney, blood first passes through the afferent artery to the capillary formation called a glomerulus and is collected in the Bowman's capsule, which filters the blood from its contents—primarily food and wastes. After the filtration process, the blood then returns to collect the food nutrients it needs, while the wastes pass into the collecting duct, to the renal pelvis, and to the ureter, and are then secreted out of the body via the urinary bladder.

Faeces

Sweat

Breath

Kidney Stones

Scientifically, masses referred to as a renal calculus or nephrolith, or more commonly, “kidney stones,” are solid masses of crystals that may be a variety of shapes, sizes, and textures, that can reside within one or both of the kidneys. [8] Kidney stones form when the balance is off between the concentration of substances that pass through urine, and the substances that are supposed to dissolve them. When substances are not properly dissolved, they have the ability to build up, and form these kidney stones. These stones are most commonly made up of substances such as calcium, cystine, oxalate, and uric acid, as these are the substances that normally would dissolve within the urine. When they do not dissolve correctly and further build up, they will commonly lodge themselves in the urinary tract and in this case, are usually small enough to pass through urine. In extreme situations, however, these stones may lodge themselves within the tube that connects the kidney and the bladder, called the ureter. In this case, they become very large in size and will most likely cause great pain, bleeding, and possibly even block the flow of urine. [9] These can occur in both men and women, and studies show that around 12% of men, and 8% of women in America will develop kidney stones within their lifetime. [10]

Treatment

In those extreme situations, in which kidney stones are too large to pass on their own, patients may seek removal. Most of these treatments involving kidney stone removal are done by a urologist a physician who specializes in the organs of the Urinary system. [11] A common way of removal is shock wave lithotripsy, in which the urologist will shock the kidney stone into smaller pieces via laser, allowing these pieces to further pass through the urine on their own, as a normal case of kidney stones. Larger, more serious cases may demand Cystoscopy, Ureteroscopy, or Percutaneous Nephrolithotomy, in which the doctor will use a viewing tool or camera to locate the stone, and based on the size or situation, may either chose to continue with surgical removal, or use the shock wave lithotripsy treatment. Once the kidney stone(s) are successfully eliminated, the urologist will commonly suggest medication to prevent future recurrences. [8]

Pyelonephritis

Pyelonephritis is a type of urinary tract infection that occurs when bacteria enters the body through the urinary tract. It causes an inflammation of the renal parenchyma, calyces, and pelvis. [12] There are three main classifications of pyelonephritis: acute, chronic and xanthogranulomatous.

Acute Pyelonephritis

In acute pyelonephritis, the patient experiences high fever, abdominal pain and pain while passing urine. Treatment for acute pyelonephritis is provided via antibiotics and an extensive urological investigation is conducted to find any abnormalities and prevent recurrence. [13]

Chronic Pyelonephritis

In chronic pyelonephritis, patients experience persistent abdominal and flank pain, high fever, decreased appetite, weight loss, urinary tract symptoms and blood in the urine. Chronic pyelonephritis can also lead to scarring of the renal parenchyma caused by recurrent kidney infections. [14]

Xanthogranulomatous Pyelonephritis

Xanthogranulomatous pyelonephritis is an unusual form of chronic pyelonephritis. It results in severe destruction of the kidney and causes granulomatous abscess formation. Patients infected with Xanthogranulomatous pyelonephritis experience recurrent fevers, anemia, kidney stones and loss of function in the affected kidney. [14]

Treatment

A urine culture and antibiotics sensitivity test is issued for patients who are believed to have pyelonephritis. Since most cases of pyelonephritis are caused from bacterial infections, antibiotics are a common treatment option. Depending on the species of the infecting organism and the antibiotics sensitivity profile of the organism, treatments may include fluoroquinolones, cephalosporins, aminoglycosides, or trimethoprim individually or in combination. [15] For patients with xanthogranulomatous pyelonephritis, treatment might include antibiotics as well as surgery. Nephrectomy is the most common surgical treatment for a majority of cases involving xanthogranulomatous pyelonephritis. [14]

Epidemiology

In men, roughly 2-3 cases per 10,000 are treated as outpatients and 1 in 10,000 cases require admission to the hospital. In women, approximately 12–13 in 10,000 cases are treated as outpatients and 3-4 cases are admitted to a hospital. [16] The most common age group affected by Xanthogranulomatous pyelonephritis is middle-aged women. [17] Infants and elderly are also at an increased risk because of hormonal and anatomical changes. [18]


How does blood flow through my kidneys?

Blood flows into your kidney through the renal artery. This large blood vessel branches into smaller and smaller blood vessels until the blood reaches the nephrons. In the nephron, your blood is filtered by the tiny blood vessels of the glomeruli and then flows out of your kidney through the renal vein.

Your blood circulates through your kidneys many times a day. In a single day, your kidneys filter about 150 quarts of blood. Most of the water and other substances that filter through your glomeruli are returned to your blood by the tubules. Only 1 to 2 quarts become urine.

Blood flows into your kidneys through the renal artery and exits through the renal vein. Your ureter carries urine from the kidney to your bladder.


How much salt, how much water, and our amazing kidneys

Salt, the one we put on food, is composed almost exclusively of sodium chloride (NaCl) that very easily dissolves in water into positively charged sodium (Na+) and negatively charged chloride (Cl-) ions. And there is something very special and unique about these ions: in our blood, Na+ and Cl- are present in the highest concentrations and maintained in the narrowest of ranges. This is very revealing, and means, quite plainly, that sodium and chloride are the most important extracellular electrolytes. This is a simple fact. Now, forget everything you’ve heard, been told, or read about salt being bad for you, and consider this:

Our blood is made of red blood cells (45%) and white blood cells and platelets (0.7%) floating in blood plasma (54.3%). Blood plasma shuttles nutrients to cells around the body and transports wastes out. It consists of 92% water, 8% specialised mostly transporter proteins, and trace amounts of solutes (things dissolved or floating in it). And although circulating in trace amounts, the solutes—especially sodium—are vital. The concentration of solutes in blood plasma is around 300 mmol/l (don’t worry about the units for now). In the highest concentration of all is sodium at 140 mmol/l. In the second highest concentration of all is chloride at 100 mmol/l. The sum of these is 240 mmol/l. So, from these numbers alone, we see that blood plasma is more or less just salty water.

Don’t you find this amazing? Don’t you find it amazing that nobody has ever told you this straight out in this way? And isn’t it amazing that we have been and continue to be told to avoid eating salt because it is bad for us: that it causes hypertension that predisposes us to heart disease? It really is completely amazing and ridiculous and also rather sad. But misunderstandings of this kind are unfortunately much more common than they should, as you may remember from What about cholesterol and Six eggs per day for six days: cholesterol?, but also from Minerals and bones, calcium and heart attacks and A diabetic’s meal on Air France. As you will understand for yourself in a few moments, the problem is not too much salt the problem is not enough water:

Hypertension is not caused by excessive salt consumption. It is caused primarily by chronic dehydration, magnesium deficiency, and calcification.

Taking a look at the other electrolytes, bicarbonate (HCO3-), the primary pH regulator, is the third most highly concentrated molecule in plasma at 20 mmol/l. Potassium (K+) is the fourth at 4-5 mmol/l, then calcium (Ca 2+) and magnesium (Mg 2+) both at about 1 mmol/l. Therefore, the concentration of sodium in the blood is 7 times higher than that of bicarbonate, 40 times higher than that of potassium, and about 140 times higher than that of calcium and magnesium. And as with everything else in our body’s exquisite physiology, there are very good reasons for this:

Every cell in every tissue and in every organ of our body relies on an electrical potential difference between the fluid inside the cell membrane and the fluid outside of it in order to function: produce energy and transport things in and out. This is particularly important in active “electrical” tissues such as muscles and nerves, including neurones, that simply cannot work—cannot contract and relax in the case of muscle fibres, and cannot fire off electrical pulses in the case of nerve fibres and neurones—without a well-maintained and stable potential across the cellular membrane.

This resting potential across the membrane results from the delicate balance of the equilibrium potential and relative permeability through the cellular membrane of the three most important ions: Na+, K+ and Cl-. The potential is maintained by the sodium-potassium pump: a specialised protein structure in the membrane that ensures the concentration of potassium (K+) stays low outside the cell and high inside the cell, and conversely, the concentration of sodium (Na+) stays high outside the cell and low inside. This is the main reason sodium is so important and why it is so carefully monitored and scrupulously reabsorbed by the kidneys, but there are plenty more.

Obviously, this is not an accident. Nothing about the way our body functions is an accident, and no matter how well a particular physiological function or mechanism is understood or not, we can be confident that it is as perfect and finely tuned as it can be because each and every bodily function is the result of adaptations and refinements over billions of years of evolution. This is not a typo: I really did mean to write billions of years. Because every single cell of which we are made has evolved from all of its predecessors as far back as the very first organic molecules that eventually organised in the very first cell: a group of more or less self-organising organelles that developed a symbiotic relationship with one another just because it benefitted them in some way, and found it safer to cluster together behind a fatty membrane through which they could interact with the outside on their own terms.

The aim of every single self-organising entity, from the simplest virus, bacterium or organelle like the mitochondria (our cellular energy-production furnaces), to highly specialised cells in the brain, in the liver or lining a part of the microscopic nephron tubule of one of the millions of these specialised filtering units in our kidneys, to largest groupings of cells in tissues, organs and systems of organs, has always been and always will be the same: survival. Therefore, to understand living systems objectively we have to understand them from the fundamental perspective of the cell itself, the tissue, the organ and the system of organs itself because every adaptation it undergoes is always aimed at improving its own odds of survival. It is very important to keep this in mind and know that everything that happens in a living system always does so in relation to something else and always for good reason, even when we don’t understand the reason, which in itself is also very important to remember.

I use this opportunity to whole-heartedly recommend Lewis Dartnell’s book Life in the universe. Almost every page for me was a delightful discovery of things I was unaware of and found the book truly illuminating.

Coming back to salt, even though we look mostly at sodium and chloride that are the principal constituents of any kind of salt we put on our food, I very strongly recommend always and exclusively using a real salt: any kind of unrefined sea salt (French, cold water, Atlantic salt is particularly clean and rich in trace minerals), Himalayan salt, Smart Salt or Real Salt (the last two are registered trade marks and very rich in trace minerals). On the contrary, I strongly discourage eating chemically manufactured table salt or even refined sea salt, which are not only stripped of trace minerals found in natural, unrefined salts, but contain varying amounts of chemical additives such as whitening agents, for instance.

Unrefined sea salt from the Atlantic coast – Sel de Guerande.

Now, without regard for polemical disputes, pseudo-scientific discussions and debates, or otherwise unfounded views and opinions about salt, can we answer the simple question: how much salt should we generally eat? I believe we can, but although it may seem so, it is not that simple a question. So let’s first ask a simpler one:

How do we make a solution with the same concentration of sodium and chloride as our blood plasma?

To answer this our approach is simple: use the mean concentrations of sodium and chloride in the blood to calculate how much salt we need to match these such that drinking our salt water solution will neither increase nor decrease their concentration. It might seem a little technical at first, but bear with me, it is in fact quite simple.

This approach is rather well motivated physiologically because the kidneys’ primary function is to maintain blood pressure and concentration of electrolytes—sodium above all others, and each within its typically narrow range of optimal concentration—while excreting metabolic wastes. The kidneys do this by efficiently reabsorbing most of the water and electrolytes from the large volume of blood that goes through them continuously throughout the day and night, getting rid of as much as possible of the metabolic wastes, and carefully adjusting the elimination of ‘excessive’ amounts of water and electrolytes. (You will soon understand why I placed quotation marks around the word excessive.) Let’s start.

You already know that the mean concentration of sodium in the blood is 140 mmol/l. What we haven’t mentioned is that it must be maintained in the range between 135 to 145 mmol/l. You also know that the mean concentration of chloride is 100 mmol/l, and it must be maintained between 95 and 105 mmol/l. The atomic mass of Na is 23, hence one mole (abbreviated mol) is 23 g, and thus one millimole (abbreviated mmol) is 23 mg. The atomic mass of Cl is 35.5, hence one mole is 35.5 g, and therefore one millimole is 35.5 mg. The molecular mass of NaCl is the sum of the atomic masses of Na and Cl, which implies that one mole of NaCl is 58.5 g, and a millimole is 58.5 mg. (A mole is the amount of substance that contains 6吆^23, Avogadro’s number, elementary entities, in this case, atoms. The molar mass is the same as the atomic or molecular mass.)

Multiplying the concentrations in mmol/l by the molar mass in mg/mmol we get the concentration in mg/l. For Na this equals 140 x 23 = 3220 mg/l or 3.22 g/l, and for Cl it is 100 x 35.5 = 3550 mg/l or 3.55 g/l. This is the mean concentration of sodium and chloride there is in our blood. For a small person like me, weighing, say, 56 kg, there are 4 litres of blood that contain a total of 13 g of Na and 14 g of Cl. This is equivalent to about 2 tablespoons of salt.

It is important to note that this is truly quite a lot in comparison to other ions or molecules in our blood. Glucose, for example, which many—probably most people—mistakenly think as the ‘energy of life’, giving it such great importance, is ideally maintained around 80 mg/dl or 0.8 g/l. This is, therefore, also the amount we would need to add to our salt and water solution to make it have, in addition to that of the salt, the same concentration of glucose as that of our blood. And 0.8 g/l for 4 litres of blood makes a total of 3.2 g of glucose in that (my) entire blood supply. This is about 10 times less than the amount of salt! What does this tell you about their relative importance in our system?

Now, given that Cl (35.5) is heavier than Na (23), NaCl will have a higher mass fraction of Cl: its mass will be 60% chloride (35.5/58.5) and 40% sodium (23/58.5). This just means that 10 g of NaCl or salt has 6 g of Cl and 4 g of Na. So to get 3.22 g of sodium, we need 8 g of sodium chloride, which provides 4.8 g of chloride.

The simple conclusion we draw from this calculation is that dissolving a somewhat heaping teaspoon of salt in one litre of water gives a solution that has the same concentration of sodium as that of our blood (with a little extra chloride).

Does this mean that we should generally drink such a salt and water solution? No, I don’t think so. Are there times when we should? Yes, I believe there are. But say we drink 4 litres per day, 8 g of salt per litre adds up to 32 g of salt just in the water we drink! If we add even half of this amount to our food, we are looking at about 50 g of salt per day! Isn’t this utterly excessive, especially since we are told by the medical authorities to avoid salt as much as possible, with some people today consuming nearly no salt at all? (This article here takes a sobering look at the evidence—actually, the lack thereof—of the claimed benefits of salt reduction.) And more questions arise: What happens when we eat less salt? What happens when we eat more? What happens when we drink less water? What happens when we drink more?

Eating more or less salt. Drinking more or less water.

Remember that the kidneys try very hard to maintain the concentration of solutes in blood plasma—to maintain plasma osmolarity. Also remember that sodium is by far the most important in regulating kidney function, and it is also in the highest concentration. It is nonetheless total osmolarity that the kidneys try to keep constant, and besides sodium, the other important molecule used to monitor and maintain osmolarity by the kidneys is ureathe primary metabolic waste they are trying to eliminate.

As an aside to put things in perspective about the importance of sodium, plasma osmolarity is typically estimated by medical professionals using the sum of twice the concentration of sodium with that of urea and glucose: calculated osmolarity = 2 Na + urea + glucose (all in mmol/l). Since sodium is typically around 140 mmol/l whereas glucose is less than 5 mmol/l and urea about 2.5 mmol/l, it’s obvious that we could just forget about the latter two whose contribution is less than 3% of the total, and look exclusively at sodium concentration (2 Na = 280 glucose + urea = 7.5, so their contribution is 7.5/(280+7.5) = 2.6%).

Eating anything at all, but especially salt or salty foods, raises plasma osmolarity. In response—to maintain constant osmolarity—the kidneys very efficiently reabsorb water and concentrate the urine. Drinking water dilutes the blood and therefore lowers its osmolarity. In response, the kidneys very scrupulously reabsorb solutes and eliminate water, hence diluting the urine.

If we eat nothing and just drink plain water, beyond the body’s minimum water needs, every glass will dilute the blood further and thus cause the kidneys to try to retain more of the sodium while eliminating more of the water. We are drinking quite a lot, but as the day progresses, we are growing more thirsty. We drink more but go to the bathroom more frequently, our urine grows more diluted, and by the end of the day we find ourselves visibly dehydrated, with chapped lips and dry skin. This seems paradoxical in that while drinking water, we are getting increasingly dehydrated. But it is not paradoxical. It is simply the consequence of the kidneys doing their work in trying to maintain constant blood plasma concentrations of sodium (and solutes). For those of you who have fasted on plain water for at least one day, you mostly likely know exactly what I’m talking about. For those who have not, you should try it and experience this first hand for yourselves. Avoiding dehydration in this case is simple: eat salt to match water intake.

If, on the other hand, we do not drink, then the blood gets more and more concentrated, the concentration of sodium and other ions, urea, and everything else for that matter, rises with time, and the kidneys keep trying, harder and harder with time, to maintain the osmolarity constant by retaining as much as they possibly can of the water that is present in the blood. You might think: why not just eliminate some of the solutes to lower their excessively high concentration? But eliminating solutes can only be done through the urine, which means getting rid of water that, in this state of increasing dehydration, is far too precious, and the kidneys therefore try to retain as much of it as possible, hence concentrating the urine as much and for as long as possible to make full use of the scarce amount of water that is available for performing their functions. But here is a crucial point to understand and remember:

In order to reabsorb water, the kidneys rely on a high concentration of solutes—hyperosmolarity—in the interstitial medium through which passes the tubule carrying the filtrate that will eventually be excreted as urine. This is how water can be reabsorbed from the filtrate: the higher the difference in concentration, the more efficient the reabsorption. If there is plenty of excess salt—sodium and chloride ions—then these solutes is what the kidneys prefers to use to drive up and maintain the hyperosmolarity of the interstitial medium, and urea can be excreted freely. If, however, there is a scarcity of sodium and chloride ions, then the kidneys will do everything to reabsorb as much of the precious ions that are in circulation to maintain adequate concentrations of these in the bloodstream, and at the slightest sign of water shortage and dehydration—to ensure the hyperosmolarity of the interstitial medium for maximum water reabsorption—the kidneys will begin to recycle urea, excreting progressively less of it as dehydration increases.

Most of you will have experienced a long day walking around, maybe while on a trip visiting a city, during which you did not drink for several hours. You might have also noticed that you probably didn’t go to the bathroom either, which you may have found unusual compared to the frequency with which you usually go pee when you’re at home or at work. You will have noticed that your mouth was drier and drier as the hours passed, but also that you felt more and more tired, heavy-footed and without energy. Eventually it struck you just how thirsty you were, or you were finally able to find water to drink, and drank to your heart’s content. As you drank, you might have felt a surge of energy within as little as a minute or two or even immediately following the first few sips. Soon after, you finally did go to the bathroom, and noticed how incredibly dark and strong smelling your urine was. Now you understand what was happening in your kidneys, why you didn’t go pee for these long hours, why your urine was so dark and smelled so strong. However, the reason why you felt your energy dwindle as the hours passed, and then return when you drank is still unclear.

Water in the blood regulates its volume. And volume in a closed system determines internal pressure. Our circulatory system is a closed system in the sense that there are no holes where blood either goes in or comes out. Yet at the same time it is not a closed system because water enters and leaves the system: it enters the bloodstream through the wall of the intestines, and leaves it through the kidneys and out into the urine. All physiological functions depend intimately on blood pressure: whether it is shooting up through the roof as we face a huge brown bear towering over us and growling at the top of its lungs, and priming us in this extremely stressful fight-or-flight situation for some kind of high-energy reaction in response, or whether it is as low as it can be during our most soothing and restful sleep deep into the night, when the body is repairing and rebuilding itself. And what is the primary regulator of blood pressure? The kidneys.

I will address the details of how the kidneys function and regulate pressure and osmolarity in another post. For now, what is relevant to understand why your energy faded as the hours passed or, more precisely, as the body got progressively more dehydrated, is straight forward:

As water content decreases, blood volume decreases. As the volume decreases, blood pressure drops. And as blood pressure drops, energy levels go down. It’s as simple as that.

It does not help that as soon as the kidneys detect dehydration and drop in pressure, they release hormones to provoke the contraction of the blood vessels in order to counter the pressure drop. This works to a great extent, but since the arteries and veins are constricted, blood flow throughout the body decreases, which in turn contributes significantly to our feeling increasingly heavy-footed and sleepy. With every passing minute, dehydration increases, pressure decreases, blood vessels contract more and our energy level drops further, to the point where we just want to sit down, or even better, lie down, right here on this park bench, and have a long nap.

Interesting, isn’t it? And here again there is nothing strange or paradoxical in this self-regulating mechanism that eventually puts us to sleep as we get increasingly dehydrated. It is simply the consequence of the kidneys doing their work in trying to maintain constant osmolarity and blood pressure. Avoiding dehydration in this case is even simpler: drink water.

If you’ve read this far, you know that both solutions to prevent dehydration are intimately linked: if we don’t drink enough water we get dehydrated, but if we drink too much water without eating salt we also get dehydrated. So let’s now ask another question:

Precisely how much water?

An adult human being needs on average a minimum of 3 litres of water per day to survive for more than a few days (Ref). This depends on climate and level of activity and a bunch of other factors, but in general the range is well established to be between 2 litres in cooler and 5 litres per day in the hottest climates. As suggested from our previous considerations, minimum water intake is also related to salt and food intake. And although this was obvious to me from my own experience of fasting rather regularly between 1 and 3 days at a time, I had not read about it. But as it turns out, the NRC and NAS both (independently) estimated minimum water intake as a function of food intake to be between 1 and 1.5 ml per calorie. For a diet of 2000 calories this would amount to between 2 and 3 litres. But this obviously does not mean that if we don’t eat anything, we don’t need any water! So, what is the very strict minimum amount of water the body needs before physiological functions break down? The short answer is 1.1 litres. For the slightly longer answer, here is a excerpt from page 45 of The Biology of Human Survival:

If obligatory losses are reduced to an absolute minimum and added up, the amounts are 600 milliliters of urine, 400 milliliters of insensible skin loss, and 200 milliliters of respiratory water loss, a total of 1.2 liters. Because maximum urine osmolarity is 1200 milliosmoles/liter, if diet is adjusted to provide the minimum solute excretion per day (about 600 mOsmol), minimum urine output may fall, in theory, to 500 milliliters per day and maitain solute balance. Hence, the absolute minimum water intake amounts to just more than 1 liter (1.1) per day.

(This is also taught in renal physiology lectures such as this one. If you are interested, you will learn a lot from this longer series of 13 segments on urine concentration and dilution here, as well as from this series of 7 segments on the renin-angiotension-aldosterone system here. I found all of them very instructive.)

Keep in mind that 1100 ml of water per day is the very bare minimum for survival, and that there are absolutely no other water losses: basically, you have to be lying, perfectly calm and unmoving at an ideal room temperature where you are neither hot nor cold, not even in the slightest. That’s not particularly realistic unless you’re in a coma. And to show just how extreme it is, let’s see how much of the water the kidneys need to reabsorb to make this happen:

For someone like me weighing 57 kg, the mass of blood is 57*7% = 4 kg. Since the density is almost equal to that of water, 4 kg corresponds to 4 litres. Of this, we know that plasma accounts for a little more than half (54.7%) by volume which makes 2.2 litres, and since plasma is 92% water, the volume of free water in the blood supply is almost exactly half: 2 litres. Blood flow through the kidneys is, on average, around 1.2 l/min. This amounts to more than 1700 litres per day, and means that for 4 litres of blood in the body, every drop of blood goes through the kidneys 425 times in 24 hours, each and every day.

In the kidneys the first step in filtration is the “mechanical”, particle-size-based separation of the blood’s solids from its liquid component. Water makes up half the blood volume, and therefore represents half the flow through the kidneys: 0.6 l or 600 ml/min (850 litres per day). But only 20% of the total flow goes through nephron filtration, which makes 120 ml/min. In the extreme case we are considering, urine output is taken to be 500 ml in 24 hours, equivalent to 20.83 ml/hour or 0.35 ml/min (500 ml/24 h/60 min). Therefore, to achieve this, the kidneys must reabsorb 119.65 ml of the 120 ml flowing through them every minute. This translates to an astounding 99.7% reabsorption efficiency! I’m very skeptical that your average person’s (generally compromised) kidneys could achieve this, but the point was to quantify how extreme this situation at the limit of human survival really is, and as you can see, it is indeed as extreme can be.

Also, keeping in mind that these minimum vital physiological water losses in these circumstances would occur at a more or less uniform rate throughout the day, it would probably be much better to drink a little at regular intervals during our walking hours than to drink everything at once and nothing else during the remaining 24 hours. But what would be the ideal rate at which we should replenish our water in these extreme circumstances?

Assuming the theoretically minimum combined water losses of 1100 ml are lost evenly over the course of the 24 hours, this corresponds to a water loss rate of 0.76 ml/min (1100 ml/24 h/60 min). This is therefore the ideal rate at which to replenishing it. In practice, we may not have an IV system to do this for us, and we will probably be sleeping long nights as our heart rate and blood pressure will have hit rock bottom. Drinking 1100 ml in 11 hours (to work with round numbers) could be done by taking 100 ml, (half a small glass), every hour. This would be the simplest and most reasonable way to maintain solute balance as best we can.

Naturally, with such a minimal water intake, the kidneys are struggling to maintain osmolarity by retaining as much water as possible. Any additional intake of salt (or food) would make things worse in the sense that it would raise the concentration of sodium (and solutes) in the blood whose balance the kidneys will not be able to maintain without additional water. But remember that eating a 200 g cucumber, for example, supplies nearly no calories as it contains virtually no sugar, fat or protein, while proving almost 200 g (ml) of water. And that, conversely, any drink containing caffeine or alcohol will actually dehydrate as those substances are diuretic and cause the excretion of free water.

A somewhat more realistic scenario is one in which we are not eating, but very moderately active at comfortable temperatures. In this case, most experts would agree that the minimum water requirements would be around 2 litres per day. Since we are fasting, these additional water needs are due to greater water losses through evaporation and physiological activity not to offsetting increased water needs due to food consumption. Consequently, we should ideally drink about 10 glasses of 200 ml, one approximately every hour from 7h to 19h, and we should not eat any salt.

More realistic but still not so common, is that you are doing a 24 hour fast. The purpose of the fast is to give a break to the digestive system, rehydrate bodily tissues, stimulate more fat burning and flush toxins out of the system. Say we drink 4 litres instead of the minimum of 2. In this case we should, in fact, eat some salt in order to ensure good hydration of tissues by supplying plenty of water through a well hydrated bloodstream without diluting the sodium and thus causing the kidneys to excrete more water. And this brings us back to the basic question that set us on this rather long investigation:

Precisely how much salt?

But you already know the answer to this question: 1 teaspoon per litre in 2 of the 4 litres. Because we don’t drink during the night for about 12 hours, the body inevitably gets dehydrated. Therefore, the best strategy is to start with plain water to rehydrate the concentrated blood and bodily tissues dehydrated from the night, and end with a litre of plain water in preparation for the dry night coming. You should take the equivalent of 1 generous teaspoon of salt with each of the additional litres of water during the day. This will ensure proper hydration of tissues by preventing excessive dilution of blood sodium levels, and maximum urea excretion. Excess sodium, chloride and any other electrolyte will be readily excreted in the urine.

Finally, the far more realistic scenario and, in fact, the one that for most of us is the everyday, is that we are normally active and eating around 2000 calories a day, typically over the course of about 12 hours. In this case we need the basic 2 litres to offset minimum evaporation and physiological losses, and between 2 and 3 litres to offset the 2000 calories. This makes between 4 and 5 litres, 2 of which must be plain water, and 2 or 3 of which must be matched by a good teaspoon of salt per litre that will most naturally, and maybe also preferably, be taken with the food.

Keep in mind that this is the total salt requirements and many prepared foods contain quite a lot already. The hotter or drier the climate, the more water we need. The more we exercise, the more water and the more salt we need. The more we sweat, the more water and the more salt we need. The more stress we experience, the more water and the more salt we need. And in all of these cases, we also need a lot more magnesium.

By the way, it is interesting but not surprising that this conclusion on the amount of salt per day: about 10-15 g, is also the recommendation of the late Dr Batmanghelidj, the “Water doctor”, as well as that of Drs Volek and Phinney, the “Low-Carb doctors” (see References for details), although the former emphasises the importance of an abundant water intake, while the latter hardly mention it if at all.

So this is it. We know how much water we should generally drink, and we know how much salt we should generally eat:

We should always drink the bare minimum of 2 litres per day. Ideally we should drink 4-5 litres every day. If for some reason we drink 2 litres or less, we should not take any salt (or food for that matter!). If we drink more than 2 litres, we should match each additional litre of water with 1 teaspoon of salt, taking into account the salt contained in the food we eat. It is always better physiologically to drink more than to drink less. And remember that we hydrate most effectively on an empty stomach by drinking 30 minutes before meals.


Molecular 'switch' turns precursors into kidney cells

Kidney development is a balancing act between the self-renewal of stem and progenitor cells to maintain and expand their numbers, and the differentiation of these cells into more specialized cell types. In a new study in the journal eLife from Andy McMahon's laboratory in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, former graduate student Alex Quiyu Guo and a team of scientists demonstrate the importance of a molecule called &beta-catenin in striking this balance.

&beta-catenin is a key driver at the end of a complex signaling cascade known as the Wnt pathway. Wnt signaling plays critical roles in the embryonic development of multiple organs including the kidneys. By partnering with other Wnt pathway molecules, &beta-catenin controls the activity of hundreds to thousands of genes within the cell.

The new study builds on the McMahon Lab's previous discovery that Wnt/&beta-catenin can initiate progenitor cells to execute a lengthy and highly orchestrated program of forming structures in the kidney called nephrons. A healthy human kidney contains a million nephrons that balance body fluids and remove soluble waste products. Too few nephrons results in kidney disease.

Previous studies from the UT Southwestern Medical Center laboratory of Thomas Carroll, a former postdoctoral trainee in the McMahon Lab, suggested that Wnt/&beta-catenin signaling plays opposing roles in ensuring the proper number of nephrons: promoting progenitor maintenance and self-renewal, and stimulating progenitor cell differentiation.

"It sounded like Wnt/&beta-catenin is doing two things -- both maintenance and differentiation -- that seem to be opposite operations," said Guo. "Therefore, the hypothesis was that different levels of Wnt/&beta-catenin can dictate different fates of the nephron progenitors: when it's low, it works on maintenance when it's high, it directs differentiation."

In 2015, it became more possible to test this hypothesis when Leif Oxburgh, a scientist at the Rogosin Institute in New York and a co-author of the eLife study, developed a system for growing large numbers of nephron progenitor cells, or NPCs, in a Petri dish.

Relying on this game-changing new system, Guo and his collaborators grew NPCs, added different levels of a chemical that activates &beta-catenin, and saw their hypothesis play out in the Petri dishes.

They observed that high levels of &beta-catenin triggered a "switch" in part of the Wnt pathway that relies on another family of transcription factors known as TCF/LEF. There are two types of TCF/LEF transcription factors: one type inhibits genes related to differentiation, and the other activates these genes. In response to high levels of &beta-catenin, the "activating" members of TCF/LEF switched places with the "inhibiting" members, effectively taking charge. This "switch" triggered NPCs to differentiate into more specialized types of kidney cells.

When they looked at low levels of &beta-catenin, they saw NPCs self-renewing and maintaining their populations, as expected. However, they were surprised to learn that &beta-catenin was not engaged with any of the known genes related to self-renewal and maintenance.

"&beta-catenin does something," said Guo. "That is for sure. But how it does it is kind of mysterious right now."

After publishing these results in eLife, Guo earned his PhD from USC, and began his postdoctoral training at UCLA. Helena Bugacov, a current PhD student in the McMahon Lab and a co-author of the eLife study, is now taking the lead in continuing the project -- which has implications far beyond the kidney field, due to the broad role of Wnt throughout the body.

"Understanding how Wnt regulates these two very distinct cell outcomes of self-renewal and differentiation, which is very important for kidney development, is also important for understanding the development of other organs and adult stem cells, as Wnt signaling plays important roles in almost all developmental systems," said Bugacov. "There is also a lot of attention from cancer researchers, as this process can go awry in cancer. Many therapeutics are trying to target this process."

She added, "The more we know about things, the better we can inform work on developing human kidney organoid cultures, which can be more readily used to understand problems in human health, regeneration and development."


The Health Impact of a Renal Light-Dark Cycle

What does this new chronobiology research mean for average people? While this may seem like a small discovery, better knowledge of the circadian rhythm of kidneys may affect health care in a variety of ways. For example, blood pressure and cardiovascular function are dependent on the electrolyte and fluid balance maintained by the kidneys. High blood pressure can cause renal damage, which in turn creates higher blood pressure in an endless cycle. In addition, many drugs are excreted by the kidneys. If kidneys are processing these drugs differently throughout the day, adjusting doses or the timing of medications can increase healing, decrease side effects and reduce the chances of overdose or toxicity.

The kidneys affect many aspects of our bodies, keeping blood clean and balanced so it can effectively deliver nutrients and excrete waste. Understanding the innate light-dark cycles of these tiny organs can improve health care for a variety of diseases.

You may also be interested in.

A new study finds that there is a link between sleep disruptions and epilepsy, suggesting&hellip

Could an infection hit you hardest if you're exposed at certain times of day? New&hellip

Many of us have experienced the havoc resulting from a change in one's circadian rhythm.&hellip



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