Physiology of digestion. Physiology of thermoregulation. Physiology of kidneys.

 

Many people spend a third of their time consciously trying to control how to get food into their digestive tracts and another third thinking about how that food is doing when it gets into their digestive tracts and another third of their time consciously trying to control how to get their food intake out of their digestive tracts. However, once food is swallowed, the conscious ability to control the passage of food is almost completely lost. When the food reaches the point of elimination some conscious control is again reestablished in the digestive system. The gastrointestinal track or as people call it, the digestive system, has the main purpose of break down food, both solid and fluid into sustenance for the various tissues and systems in the body. A normal digestive tract squeezes the utmost benefit from what it eats. Feces are the products left over when the body has selected everything that is of use from the food that has been eaten.The digestive system distance ranges from the mouth to the bottom of the trunk, which when we look at it, seems like no more than two or three feet, but is really about 30 feet and like a railway station consisting of signals, checkpoints, and control devices in a turning, zigzagging, coiling track system.

From the moment the three main types of food-carbohydrates, fats and proteins-enter the mouth, they are exposed to chemical and mechanical actions that begin to break them apart so that they can be absorbed through the intestinal walls into the circulatory system.

 

Taste Receptors

A very large number of molecules elicit taste sensations through a rather small number of taste receptors. Furthermore, it appears that individual taste receptor cells bear receptors for one type of taste. In other words, within a taste bud, some taste receptor cells sense sweet, while others have receptors for bitter, sour, salty and umami tastes. Much of this understanding of taste receptors has derived from behavioral studies with mice engineered to lack one or more taste receptors.

The pleasant tastes (sweet and umami) are mediated by a family of three T1R receptors that assemble in pairs. Diverse molecules that lead to a sensation of sweet bind to a receptor formed from T1R2 and T1R3 subunits. Cats have a deletion in the gene for T1R2, explaining their non-responsiveness to sweet tastes. Also, mice engineered to express the human T1R2 protein have a human-like response to different sweet tastes. The receptor formed as a complex of T1R1 and T1R3 binds L-glutamate and L-amino acids, resulting the umami taste.

The bitter taste results from binding of diverse molecules to a family of about 30 T2R receptors. Sour tasting itself involves activation of a type of TRP (transient receptor potential) channel. Surprisingly, the molecular mechanisms of salt taste reception are poorly characterized relative to the other tastes.

Taste is a chemical sense which is detected by special structures called taste buds, of which we all have about 10,000, mainly on the tongue with a few at the back of the throat and on the palate. Taste buds surround pores within the protuberances on the tongue’s surface and elsewhere. There are four types of taste buds: these are sensitive to sweet, salty, sour and bitter chemicals. All tastes are formed from a mixture of these basic elements.

Many different tastes can be distinguished because of the combination of taste and the more discriminating sense of smell. The sense of smell is estimated to be about 10,000 times more sensitive than the sense of taste. The two senses are very closely related. It is usually correct to say that one smells more flavours than one tastes. When the nose fails, from a bad cold for instance, 80% of the taste ability is lost. Loss of taste without loss of smell is pretty rare, but “dry mouth” can contribute because taste buds can only detect flavour when food is dissolved in saliva. Taste can also be lost as a result of damage to the taste buds themselves or damage to the cranial nerves that carry taste sensations to the brain. Full sensory appreciation of food also involves its appearance, its consistency, and its temperature.

Green represents the area where sweet taste is interpreted.

Blue interprets salty tastes.

Red detects sour tastes and yellow picks out the bitter tastes.

Observation of the Tongue

Observation of the tongue, also known as tongue diagnosis, is an important procedure in diagnosis by inspection. It provides primary information for the Chinese physicians to make diagnosis.

Physiology of the tongue. The tongue directly or indirectly connects with many zang – fu organs through the meridians and collaterals. The deep branch of Heart Meridian of Hand – Shaoyin goes to the root of the tongue ; the Spleen Meridian of Foot – Taiyin traverses the root of the tongue and spreads over its lower surface ; the Kidney Meridian of Foot – Shaoyin terminates at the root of the tongue. So the essential qi of the zang – fu organs can go upward to nourish the tongue, and pathological changes of the zang – fu organs can be reflected by changes in tongue conditions. This is why the observation of the tongue can determine the pathological changes of the internal organs.

Observation of the tongue includes the tongue proper and its coating. The tongue proper refers to the muscular tissue of the tongue, which is also known as the tongue body. The tongue coating refers to a layer of ” moss ” over the tongue surface, which is produced by the stomach qi. A normal tongue is of proper size, soft in quality, free in motion, slightly red in color and with a thin layer of white coating which is neither dry nor over moist.

The tongue is divided into four areas, namely, tip, central part, root and border. The tip of the tongue often reveals the pathological changes of the heart and lung ; its border reveals those of the liver and gallbladder ; its central part reveals those of the spleen and stomach ; and its root reveals those of the kidney. This method of diagnosing the pathological changes of the zang – fu organs by dividing the tongue into corresponding areas is clinically significant.

Stomach

Experimental method of studying of stomach secretion (Method of Basov – during the operation on dogs put the fistula in stomach. It connect stomach with the external environment. During eating the stomach juice go out through this fistula, but it has food and saliva. Method of Pavlov – method of “imaging eating” – during the operation on dogs put 2 fistulas: in esophagus and stomach. During eating the food go out through the esophagus fistula, that is way we have only juice. Method of Geydengine – a little stomach – to apart a little part of stomach, in which cut n.vagus. In this case we may to study humoral stimulation. Method of Pavlov – to separate little stomach from whole organ by 2 layers of mucous. In this case presents all regulatory mechanisms.)

c) Clinical method of stomach investigation (Gastroscopy, stomach sound, ultrasonic investigation, electrogastrography, pH-metry, determine helycobacter pylory.)

About 10 inches down the esophagus, the swallowed food or bolus is now fairly well minced and turned into a pulpy mass as it passes into the stomach. The function of the stomach is best described as a food processing unit (similar to one you may have in your kitchen) and a storage cistern. It looks like a deflated balloon when empty, but when full, it becomes about a foot long and six inches wide able to hold about two quarts of food and drink. Persons have been known, however, to live a full life with part or even all of it removed. The stomach is both chemical and mechanical. Various chemicals in the stomach like the digestive enzymes pepsin, rennin, and lipase interact to break down the food. In addition, hydrochloric acid creates suitable environment for the enzymes and assists in the digestion. Also, watery mucus provides a protective lining for the muscular walls of the stomach so it will not be digested by the acid or enzymes. The mechanical action of the muscles in the stomach constrict and relax in a continuous motion blending, whipping, and stirring the stomach’s contents into chyme, a pulpy substance that can be handled by the small intestine.

To stimulate production of duodinum gormon – secretin.)

 Phases of stomach secretion

a) Cephalic phase (This phase caused by nervous system. It has conditional and unconditional reflexes. Conditional reactions caused by appearance of food, it smell and other stimulus, which are connect with food. Unconditional influences have parasympathetic. Parasympathetic components of unconditional influences beginning from receptors of tongue and other receptors of the oral cavity. From these receptors impulses pass through the fibers of nervus trigeminus, nervus facialis, nervus glossopharyngeus, nervus vagus to the medulla oblongata. Impulses return to stomach by nervus vagus. Except neuron influences this phase has humoral influences – brunch of nervus vagus produce gormon gastrin. These phase is very shortly.)

b) Stomach phase (These phase depend from quantity of food, which are present in stomach. It has vago-vagal reflexes (by mean of central nerves system) and local – peripheral reflexes, which are closed in stomach walls. Duration of these phase is longer and quantity of juice is much. It has humoral mechanisms too (production of gastrin and histamin).

c) Intestine phase (Presence of food in the upper portion of small intestine can cause the stomach to secrete small amount of gastric juice. This probably results of gastrin are also released by the duodenal mucosa in response to distension or chemical stimuli of the same type as those that stimulate the stomach gastrin mechanism.)

Value of gastric juice secretion

In norm gastric juice secretion must be

1. Digestion in the small intestine

a) Role of duodenum in the digestive system (There are two secretor functions of pancreas – external and internal. The external secretor function of pancreas means that exsogenic cells of pancreas and ducts cells produce pancreatic juice. It helps to hydrolyzed protein to peptides and amino acids, carbohydrates to monosaccharides, lipids to the fat acids and glycerine. It neutralizes acidic chymus, which come from stomach.)

 

b) External secretor function of pancreas (The external secretor function of pancreas means that exsogenic cells of pancreas and ducts cells produce pancreatic juice).

c) Composition and property of pancreas juice (Quantity of pancreatic juice per day – 1,5-2,0 L. Reaction of it – pH =8,0-8,5. It has a big quantity of hydrocarbonates. It has near 10 % of protein – enzymes, which are act on protein, lipids and carbohydrates. Proteolytic enzymes secreted in form, which are not active, for example, trypsinogen, chymotrypsinogen. Trypsinogen activated by enzymes enterokinase (produced by the cells of mucous of duodenum) and after that it has another name – trypsin. It activates chymotripsinogen to chymotrypsin. In pancreatic juice presents another proteolytic enzymes – elastase, nuclease etc. They hydrolyzed protein to peptides and amino acids. Lipolytic enzymes – lipase and phospholipase – hydrolyzed lipids to the fat acids and glycerine. Amilolytic enzyme alpha-amilase hydrolyzed starch and glikogen to oligo-, di- and monosaccharides.)

d) Regulation of pancreas secretion (Regulation act by complex of neuro-humoral mechanisms. There are three phases of pancreatic secretion: cephalic, stomach and intestine. The first stage caused by act of nervous influences. Nervus vagus realizes this effect by means of conditioned and unconditioned reflexes. Secretion begins after 1-2 minutes of food. This juice consists of enzymes, small quantity of water and ions. Sympathetic influences have a trophic role. During the second phase there are two kinds of influences: nervous and humoral, for example, gastrin from stomach. The third phase caused by chymus contents. The main is humoral factors. In that time secrete 2 hormons – secretin and cholecystokinin-pancreasemin. Secretin stimulates production of a big quantity of juice with a high concentration of hydro carbonates and a small quantity of enzymes in ducts cells. Cholecystokinin-pancreasemin stimulates production of a less quantity of juice with a big concentration of enzymes in acinars cells.)

e) Bile production and bile secrete (Secretion of bile occur all time and increase by influences of bile acids, cholecystokinin-pancreasemin, secretin. Bile secretion in the duodenum depends from take food. It depends of nervus vagus and humoral influences – concentration of cholecystokinin-pancreasemin, secretin, fats.)

f) Composition of bile, their role in digestive processes (Composition: bilirubin, bile acids, cholesterol, leukocytes, some epitheliocytes, cristalls of bilirubin, calcium, cholesterol. The role of bile: 1. Neutrolyze the stomach acid; 2. Inhibit he act of stomach proteases; 3. Increase the activity of pancreatic lipase; 4. Emulgate the lipids; 5. Increase the absorption of fat acids, vitamins K, D, E; 6. Increase tone and motor function of intestines; 7. Decrease the activity of intestine microflora.)

g) Composition and properties of intestine juice (Composition of intestine juice: mucus, enzymes – peptidase, saccharase, maltase, lactase, lipase, immunoglobulins, leukocytes; epitheliocytes (200 g per day). pH of juice – 7,5-8,0; production per day – near 1,8 L. Functions: ending hydrolyses of all nutritive substances; protective of mucus wall; support of chymus in fluid condition; formed of base reaction of intestine contents.)

h) Cavity and membrane hydrolyses of substances (On the glicocalix of micro fibers present enzymes, which are adsorbed and digest small molecules of nutritive substances – membrane hydrolyses of substances. Cavity hydrolyses of substances provide by enzymes, which are in intestine space.)

Digestion in the large intestine

a) Composition of intestine juice and their properties (Composition of intestine juice: mucus, epithelial cells. Functions: protective from mechanical, chemical irritations; formed of base reaction of intestine contents.)

b) Role of the micro flora of big intestine (1. Ending decompose of all nutritive substances, which are do not digestive; synthesis of some vitamins – of B group, vitamin K; take place in metabolic processes.)

Small intestine

The small intestine is the longest organ of the digestive tract. It is divided up indiscriminately into three sections: the duodenum, the jejunum, and the ilium.

Duodenum

This is the place where the ultimate destruction of food digestion reaches its completion and where the acidity of chyme is nullified. The nutrients in the food eaten many hours ago have almost been diminished to molecules small enough to be absorbed through the intestinal walls into the bloodstream. Carbohydrates are diminished into simpler sugars; proteins to amino acids; and fats to fatty acids and glycerol. Enzymes are secreted by the walls of the duodenum and unite with the bile (essential for the digestion and absorption of tenacious fatty materials) and pancreatic enzymes in the duodenum.

Jejunum

Peristalsis pushes the nutrient liquid out of the duodenum into the first reaches of the jejunum. A greater number of villi , microscopic, hair like structures, begin to absorb amino acids , sugars, fatty acids and glycerol from the digested contents of the small intestine, and starts them on their way to other parts of the body. This part of the small intestine executes a digestive operation so that what is passed on to the large intestine is a thin watery substance almost completely devoid of nutrients.

Ilium

This is the place which is about a third of the small intestine. The greatest number of the estimated five or six million villi in the small intestine are found along the ilium making it the main absorption locale of the gastrointestinal tract. The villi here are always in a fretful movement: oscillating, pulsating, lengthening, shortening, growing narrower then wider, extorting every particle of nutrient.

The Liver, Gallbladder, and Pancreas

Legitimately, these three organs lie outside of the gastrointestinal tract. Nevertheless, digestive fluids from all three meet like intersections of a railway track at the common bile duct, and their movement from there into the duodenum is controlled by a sphincter muscle.

 

 

The pancreas is a producer of digestive enzymes. The gallbladder is a small reservoir for bile. The liver reproduces nutrients so that they can be used for cell-rebuilding and energy.

 

Large Intestine

There is a merger between the illium and the cecum, the first section of the large intestine. Any solid substances that flow into the large intestine through the ileocecal valve (which prevents back flow into the small intestine) are as a rule indigestible, or are bile constituents. What the cecum primarily inherits is water.
What the large intestine essentially does, other than act as a passageway for removal of body wastes, is to act as a provisional reservoir for water. There are no villi in the large intestine and peristalsis is much less forceful than in the small intestine. As water is absorbed, the contents of the large intestine change from a watery liquid and are compressed into semisolid feces. Nerve endings in the large intestine signal the brain that it is time for a bowel movement. The fecal material moves through the colon down to several remaining inches known as the rectum and out through the anus an opening controlled by the outlet valves of the large intestine.

Enzymes

Site of Enzyme Origin	Enzyme	Nutrient It Breacks Down	Product Of Enzyme Action	Place of Enzyme Action
Salivary Glands	Salivary Almalase	Carbohydrates-sugars	Simple Sugars	Mouth
Gastric glands	Pepsin	Proteins	Amino Acids	Stomach
Liver	Bile	Fats/Lipids	Emulsifide Fats	Small Intestine
Small Intestine	Maltase, Lactase, Sucrase	Carbohydrates	Simple sugars	Small Intestine
Pancrease	Trypsin, Lipase, Amylase	Proteins, Fats/Lipids, Carbohydrates	Amino acids, Glycerol/Fatty Acids, Simple Sugars	Small Intestine

Mechanical Digestion

Mechanical Digestion takes place in the mouth, where the the saliva, teeth, and tongue all play an important role in this digestive process.

Saliva

The smallest taste, smell, and anticipation of food sends signals to the brain. The brain in turn sends messages to a system of salivary glands. Saliva is essentially made up of water and begins to soften up the food so it can pass more smoothly down the throat. Besides water there is also a very special substance, an enzyme called pytalin , whose main task is to breakdown the food into simpler forms.

Teeth

The aftermath of the action of the teeth in digestion results in two outcomes: havoc and devastation. The teeth are gears to demolish chunks of food by a series of actions such as clamping, slashing, piercing, grinding and crushing. The teeth do the first drastic destruction to food in the digestive system.

Tongue

The tongue consists of four types of taste buds–salty, sweet, sour, and bitter–and is a very maneuverable and pliable arrangement of muscle. It helps to remove, and dislocate food particles in the teeth and shifts food around in the mouth in order to assist with the all important act of swallowing.

The act of swallowing food, which at this place in the system is called a bolus, brings many organs into action. As the top of your tongue presses up against the hard palate , the roof of your mouth, food is shoved to the back of the mouth. This action in turn brings the soft palate and ursula (the place at the very back of the mouth where there is a teardrop shape located) into action. They keep the food from being misguided toward the nose. Once past the soft palate, the food is in the pharynx, a train station with two tracks, one leading to the trachea (windpipe), the other to the esophagus (food tube). The epiglottis projects out from the trachea side and helps to admit free movement of air as it is swallowed and at the same time restricts entrance to the esophagus. The larynx -hyper link, provides the epiglottis with most of its muscle for movement. It applies an upward force that helps to relax some tension on the esophagus, so that food enters where it is meant to go, down the esophagus and not down the windpipe. Many people have experienced at some time or another when the swallowing action did not go as it was supposed to.

Peristalsis

This mechanical action has to do with sets of muscles that cooperate to move both liquid and solid food along the digestive tract. In other word, it pushes food along your esophagus, stomach, and intestine.. Gravitational pull is lessened in a sense when food enters the esophagus because of peristalsis. Peristalsis helps a person to swallow lying down or even standing on their head. Peristalsis has another essential task besides assisting in the movement of food through the body. It also helps to knead, agitate, and pound the solid residue that is left after the teeth or those without teeth, the gums, have done their best. Digestive Sphincters

The gastrointestinal tract is supplied with a number of muscular valves. These control and direct the quantity of food that goes through the digestive tract and inhibits the back movement of partially digested food.

1. Common characteristic of absorption process

a)Determine of notion “absorption”

Absorption is a complex of processes, which are provide transport of substances from digestive tract into internal surroundings of organism (blood, lymph, intercellular substances).

Main types of transport of nutritive substances in internal surroundings of organism are: passive and active.

b) Main types of transport of nutritive substances in internal surroundings of organism

1.Passive transport include diffusion and osmosis. This transport do not need presents of energy. In this case substances transport through the mucus shell by help of concentrative gradient. This way of transport have water, water disolved vitamins (C, B₆, B₂).

2.Active transport include pinocytosis and active transport by help of protein and energy. Active transport need energy of ATP. This way characteristic of amino acids, monosaccharids, vitamin B₁₂, ions of calcium, enzymes. Pinocytosis – by help of pynocytic bulb, where secreted enzymes for proteins hydrolysis. Products of hydrolysis adsorbed by cell.

1. ANATOMICAL BASIS OF ABSORPTION

The total quantity of fluid that must be absorbed each day is equal to the ingested fluid (about 1,5 liters) plus that secreted in the various gastrointestinal secretions (about seven liters). This comes to a total of approximately 8 to 9 liters. All but 1,5 liters of this is absorbed in the small intestine, leaving only 1,5 liters to pass through the ileocecal valve into the colon each day.

The stomach is a poor absorptive area of the gastrointestinal tract because it lacks the typical villus type of absorptive membrane and also because the junctions between the epithelial cells are tight junctions. Only a few highly lipid-soluble substances, such as alcohol and some drugs like aspirin, can be absorbed in small quantities.

The Absorptive Surface of the Intestinal Mucosa – The Villi.

The absorptive surface of the intestinal mucosa, showing many folds called valvulae conniventes (or folds of Kerckring), which increase the surface area of the absorptive mucosa about threefold. These folds extend circularly most of the way around the intestine and are especially well developed in the duodenum and jejunum, where they often protrude as much as 8 mm into the lumen.

Located over the entire surface of the small intestine, from approximately the point at which the common bile duct empties into the duodenum down to the ileocecal valve, are literally millions of small villi, which project about 1 mm from the surface of the mucosa. These villi lie so close to each other in the upper small intestine that they actually touch in most areas, but their distribution is less profuse in the distal small intestine. The presence of villi on the mucosal surface enhances the absorptive area another tenfold.

The intestinal epithelial cells are characterized by a brush border, consisting of about 600 microvilli 1 μm in length and 0,1 μm in diameter protruding from each cell. This increases the surface area exposed to the intestinal materials another 20-fold. Thus, the combination of the folds of Kerckring, the villi, and the microvilli increases the absorptive area of the mucosa about 600-fold, making a tremendous total area of about 250 square meters for the entire small intestine – about the surface area of a tennis court.

The general organization of a villus, emphasizing especially the advantageous arrangement of the vascular system for absorption of fluid and dissolved material into the portal blood, and the arrangement of the central lacteal for absorption into the lymph. Many small pinocytic vesicles, which are pinched-off portions of infolded epithelium surrounding extracellular materials that have been entrapped inside the cells. Small amounts of substances are absorbed by this physical process of pinocytosis, though, as noted later in the chapter, most absorption occurs by means of single molecular transfer. Located near the brush border of the epithelial cell are many mitochondria, which supply the cell with oxidative energy needed for active transport of materials through the intestinal epithelium. Also, extending linearly into each microvillus of the brush border are multiple actin filaments that are believed to contract and cause continual movement of the microvilli, keeping them constantly exposed to new quantities of intestinal fluid.

BASIC MECHANISMS OF ABSORPTION

Absorption through the gastrointestinal mucosa occurs by active transport and by diffusion, as is also true for other membranes.

Briefly, active transport imparts energy to the substance as it is being transported for the purpose of concentrating it on the other side of the membrane or for moving it against an electrical potential On the other hand, the term diffusion means simply transport of substances through the membrane as a result of molecular movement along, rather than against, an electrochemical gradient.

c)Absorption in the mouth cavity and stomach

In the mouth cavity absorbed water, water soluble medicines (for example, validol, nitroglycerin, adelphan, furosemid, corinfar and others). In our oral cavity, under the tongue present a big quantity of vessels. That is why all water soluble substances absorbed in this place. They go to the bloodstream, and have immediately action on our receptors. They do not go through the liver, and do not desintoxicated, that is why may be toxic effect of some substances, for example products of food, drugs.

In esophagus do not absorbed nutritive substances as a rule.

In stomach absorbed alcohol, water and small quantity of other substances.

ABSORPTION IN THE SMALL INTESTINE

d) Absorption in intestines

Normally, absorption from the small intestine each day consists of several hundred grams of carbohydrates, 100 or more grams of fat, 50 to 100 grams of amino acids, 50 to 100 grams of ions, and 7 to 8 liters of water. However, the absorptive capacity of the small intestine is far greater than this as much as several kilograms of carbohydrates per day, 500 to 1000 grams of fat per day, 500 to 700 grams of amino acids per day, and 20 or more liters of water per day. In addition, the large intestine can absorb still more water and ions, though almost no nutrients.

ABSORPTION IN THE LARGE INTESTINE

Approximately 1500 ml of chyme pass through the ileocecal valve into the large intestine each day. Most of the water and electrolytes in this are absorbed in the colon, usually leaving less than 100 ml of fluid to be excreted in the feces. Also, essentially all the ions are also absorbed, leaving only about 1 mEq each of sodium and chloride ions to be lost in the feces.

Most of the absorption in the large intestine occurs in the proximal half of the colon, giving this portion the name absorbing colon, whereas the distal colon functions principally for storage and is therefore called the storage colon.

Absorption and Secretion of Electrolytes and Water. The mucosa of the large intestine, like that of the small intestine, has a high capability for active absorption of sodium, and the electrical potential created by the absorption of the sodium causes chloride absorption as well. The „tight junctions“ between the epithelial cells of the large intestinal epithelium are much tighter than those of the small intestine. This prevents significant amounts of back-diffusion of ions through these junctions, thus allowing the large intestinal mucosa to absorb sodium ions far more completely – that is, against a much higher concentration gradient – than can occur in the small intestine.

In addition, as in the distal portion of the small intestine, the mucosa of the large intestine actively secretes bicarbonate ions while it simultaneously actively absorbs an equal amount of chloride ions in an exchange transport process. The bicarbonate helps neutralize the acidic end-products of bacterial action in the colon.

The absorption of sodium and chloride ions creates an osmotic gradient across the large intestinal mucosa, which in turn causes absorption of water.

Bacterial Action in the Colon. Numerous bacteria, especially colon bacilli, are present in the absorbing colon. These are capable of digesting small amounts of cellulose, in this way providing a few calories of nutrition to the body each day. In herbivorous animals this source of energy is very significant, though it is of negligible importance in the human being. Other substances formed as a result of bacterial activity are vitamin K, vitamin B₁₂, thiamin, riboflavin, and various gases that contribute to flatus in the colon – especially carbon dioxide, hydrogen gas, and methane. Vitamin K is especially important, for the amount of this vitamin in the ingested foods is normally insufficient to maintain adequate blood coagulation.

Composition of the Feces. The feces normally are about three-fourths water and one-fourth solid matter composed of about 30 per cent dead bacteria, 10 to 20 per cent fat, 10 to 20 per cent inorganic matter, 2 to 3 per cent protein, and 30 per cent undigested roughage of the food and dried constituents of digestive juices, such as bile pigment and sloughed epithelial cells. The large amount of fat derives mainly from fat formed by bacteria and fat in the sloughed epithelial cells.

The brown color of feces is caused by stercobilin and urobilin, which are derivatives of bilirubin. The odor is caused principally by the products of bacterial action; these vary from one person to another, depending on each person’s colonic bacterial flora and on the type of food eaten. The actual odoriferous products include indole, skatole, mercaptans, and hydrogen sulfide.

ABSORPTION OF WATER

Isosmotic Absorption. Water is transported through the intestinal membrane entirely by the process of diffusion. Furthermore, this diffusion obeys the usual laws of osmosis. Therefore, when the chyme is dilute, water is absorbed through the intestinal mucosa into the blood of the villi by osmosis.

On the other hand, water can also be transported in the opposite direction, from the plasma into the chyme. This occurs especially when hyperosmotic solutions are discharged from the stomach into the duodenum Usually within minutes, sufficient water is transferred by osmosis to make the chyme isosmotic with the plasma Thereafter, the chyme remains almost exactly isosmotic throughout its total passage through the small and large intestines.

As dissolved substances are absorbed from the lumen of the gut into the blood the absorption tends to decrease the osmotic pressure of the chyme, but water diffuses so readily through the intestinal membrane (because of large 7 to 15 A intercellular pores through the so-called „tight junctions“ between the epithelial cells) that it almost instantaneously „follows“ the absorbed substances into the blood. Therefore, as ions and nutrients are absorbed, so also is an isosmotic equivalent of water absorbed In this way not only are the ions and nutrients almost entirely absorbed before the chyme passes through the intestinal tract but so also is almost 99 per cent of the water absorbed.

e) Methods of absorptions’ investigation

1. Angiostoma (experimental method). Surgeon put stoma, aperture, on one of the gastrointestinal vessels in which absorbed nutritive substances. He add it by help of catheter of body surface. In this case he investigate absorption processes in anybody part of intestines.

In the case of angiostoma he may investigate each stage of digestion in different organs – oral cavity, esophagus, stomach, small and large intestines. He may determining the speed of absorption; quantity of different substances, which are absorbed in different part of digestive tract; components of food, which can absorbed in different part of gastro-intestinal tract; speed of bloodstream in the different part of gastro-intestinal tract, which help to absorbed some substances; mechanism of absorption in different part of gastrointestinal tract.

2. X-ray investigation (experimental or clinical method). In this case by help of different substances, for example, suspension of barium for determining motor function of gastrointestinal tract and other water-soluble substances to determining absorption. Doctor do X-ray investigation and determining place of absorption, place of increase or decrease speed of absorption, part of digestive tract, where present decrease of absorption. This method may be act on animal too, for example, if we need to determining absorption of new substances.

3. Biochemical method of investigation (experimental or clinical method). In this case laboratory assistant investigate blood, urine, saliva to content of different substances – glucose, amino acids, fat acids, lactose, mannose, sugar and others. For example, to determining pathology of carbohydrates absorption in intestines doctor laboratory assistant investigate quantity of glucose, or galactose, or lactose, or mannose in blood and urine and if he know the quantity of glucose which are coming into organism, he may value absorption of glucose, or galactose, or lactose, or mannose in digestive tract. For example, to determining pathology of sodium or potassium absorption in digestive tract doctor laboratory assistant investigate concentration of sodium or potassium in saliva, blood, urine and after that doctor may value their absorption.

4. Radioisotopic investigation (clinical method). Nurses inject intravenously radioisotop, which absorbed in digestive tract, into the organism of patient. After some time, which is necessary for investigation, doctor scan the places, where this isotop must absorbed. Then he determining the absorptive function of intestines, as he see the speed of absorption, quantity of radioisotop, which are absorbed and place of absorption of radioisotop.

Water and mineral salts

Active Transport of Sodium. Twenty to 30 grams of sodium are secreted into the intestinal secretions each day. In addition, the normal person eats 5 to 8 grams of sodium each day. Combining these two, the small intestine absorbs 25 to 35 grams of sodium each day, which amounts to about one seventh of all the sodium that is present in the body. One can well understand that whenever the intestinal secretions are lost to the exterior, as in extreme diarrhea, the sodium reserves of the body can be depleted to a lethal level within hours. Normally, this sodium is secreted and reabsorbed continually with only about 1 milliequivalent lost in the feces each day. The sodium plays an important role in the absorption of sugars and ammo acids, as we shall see in subsequent discussions.

The principles of sodium absorption from the intestine are also essentially the same as those for absorption of sodium from the renal tubules. The motive power for the sodium absorption is provided by active transport of sodium from inside the epithelial cells through the side walls of these cells into the intercellular spaces. This active transport obeys the usual laws of active transport it requires energy, and it is catalyzed by appropriate ATPase carrier enzymes in the cell membrane. Part of the sodium is transported along with chloride ions that are passively „dragged“ along by the positive electrical charges of the sodium ion. However, other sodium ions are absorbed while either potassium or hydrogen ions are transported into the lumen of the gut in exchange for the sodium ions. In the membrane of the brush border are special transport proteins that facilitate these exchanges between sodium and potassium or sodium and hydrogen.

The active transport of sodium reduces its concentration in the cell to a low value (about 50 mEq/liter). Since the sodium concentration in the chyme is normally about 142 mEq/liter (that is, approximately equal to that in the plasma), sodium moves by passive absorption from the chyme through the brush border of the epithelial cell into the epithelial cell cytoplasm. This replaces the sodium that is actively transported out of the epithelial cells into the intercellular spaces.

The next step in the transport process is osmosis of water into the intercellular spaces. This movement is caused by the osmotic gradient created by the elevated concentration of ions in the intercellular space. Most of this osmosis occurs through the „tight junctions“ between the apical borders of the epithelial cells, as discussed earlier, but a smaller proportion occurs through the cells themselves. The osmotic movement of water creates a flow of fluid into the intercellular space, then through the basement membrane of the epithelium, and finally into the circulating blood of the villi.

Absorption of Chloride Ions in the Duodenum and Jejunum. In the upper part of the small intestine chloride absorption is mainly by passive diffusion. The absorption of sodium ions through the epithelium creates electronegativity in the chyme and electropositivity on the basal side of the epithelial cells. Then chloride ions move along this electrical gradient to „follow“ the sodium ions.

„Active“ Absorption of Bicarbonate Ions in the Duodenum and Jejunum. Often, large quantities of bicarbonate ions must be reabsorbed from the upper small intestine because of the large amounts of bicarbonate ions in both the pancreatic secretion and bile. However, the bicarbonate ion is absorbed in an indirect way as follows: When sodium ions are absorbed, moderate amounts of hydrogen ions are secreted into the lumen of the gut in exchange for some of the sodium, as explained earlier. These hydrogen ions in turn combine with the bicarbonate ion to form carbonic acid (H₂CO₃), and this then dissociates to form H₂O and CO₃. The water remains part of the chyme in the intestines, but the carbon dioxide is readily absorbed into the blood and subsequently expired through the lungs. Thus, this is the so-called „active“ absorption of bicarbonate ions. It is the same mechanism that occurs in the tubules of the kidneys.

Active Absorption of Chloride Ions and Active Secretion of Bicarbonate Ions in the Ileum and Large Intestine. The epithelial cells of the ileum and of the large intestine have the special capability of actively absorbing chloride ions by means of a tightly coupled transport mechanism in which an equivalent number of bicarbonate ions are secreted. The functional role of this mechanism is to provide bicarbonate ions for neutralization of acidic products formed by bacteria – especially in the large intestine.

Various bacterial toxins, particularly those of cholera, colon bacilli, and staphylococci, can strongly stimulate this chloride-bicarbonate exchange mechanism.

Absorption of Other Ions. Calcium ions are actively absorbed, especially from the duodenum, and calcium ion absorption is exactly controlled in relation to the need of the body for calcium. One important factor controlling calcium absorption is parathyroid hormone secreted by the parathyroid glands, and another is vitamin D. The parathyroid hormone activates vitamin D in the kidneys, and the activated vitamin D in turn greatly enhances calcium absorption.

Iron ions are also actively absorbed from the small intestine. The principles of iron absorption and the regulation of its absorption in proportion to the body’s need for iron.

Potassium, magnesium, phosphate, and probably still other ions can also be actively absorbed through the mucosa. In general, the monovalent ions are absorbed with ease and in great quantities. On the other hand, the bivalent ions are normally absorbed in only small amounts; for instance, the maximum absorption of calcium ions is only 1/50 as great as the normal absorption of sodium ions. Fortunately, only small quantities of the divalent ions are normally needed by the body.

b) Products of proteins hydrolyses

Absorption of Proteins

Most proteins are absorbed in the form of amino acids. However, small quantities of dipeptides and even tripeptides are also absorbed, and extremely minute quantities of whole proteins can at times be absorbed by the process of pinocytosis, though not by the usual absorptive mechanisms.

The absorption of amino acids also obeys the principles listed above for active absorption of glucose; that is, the different types of amino acids are absorbed selectively and certain ones interfere with the absorption of others, illustrating that common carrier systems exist. Finally, metabolic poisons block the absorption of amino acids in the same way that they block the absorption of glucose.

Absorption of amino acids through the intestinal mucosa can occur far more rapidly than can protein digestion in the lumen of the intestine. As a result, the normal rate of absorption is determined not by the rate at which they can be absorbed but by the rate at which they can be released from the proteins during digestion. For these reasons, essentially no free ammo acids can be found in the intestine during digestion – that is, they are absorbed as rapidly as they are formed. Since most protein digestion occurs in the upper small intestine, most protein absorption occurs in the duodenum and jejunum.

Basic Mechanisms of Amino Acid Transport. As is true for monosaccharide absorption, very little is known about the basic mechanisms of amino acid transport. However, at least four different carrier systems transport different amino acids – one transports neutral amino acids, a second transports basic amino acids, a third transports acidic amino acids, and a fourth has specificity for the two imino acids proline and hydroxyproline. Also, the transport mechanisms have far greater affinity for transporting L-stereoisomers of amino acids than D-stereoisomers.

Amino acid transport (at least for most of the amino acids), like glucose transport, occurs only in the presence of simultaneous sodium transport. Furthermore, the carrier systems for amino acid transport, like those for glucose transport, are in the brush border of the epithelial cell. It is believed that amino acids are transported by the same sodium cotransport mechanism as that explained above for glucose transport. That is, the theory postulates that the carrier has receptor sites for both an amino acid molecule and a sodium ion. Only when both of the sites are filled will the carrier move both the sodium and the amino acid to the interior of the cell at the same time. Because of the sodium gradient across the brush border, the sodium diffusion to the cell interior pulls the amino acid to the interior where the amino acid becomes trapped. Therefore, amino acid concentration increases within the cell, and it then diffuses through the sides or base of the cell into the portal blood, probably by a facilitated diffusion process. 

c)Products of carbohydrates hydrolyses

Essentially all the carbohydrates are absorbed in the form of monosaccharides, only a small fraction of a per cent being absorbed as disaccharides and almost none as larger carbohydrate compounds. Furthermore, little carbohydrate absorption results from simple diffusion, for the pores of the mucosa through which diffusion occurs are essentially impermeable to water-soluble solutes with molecular weights greater than 100.

That the transport of most monosaccharides through the intestinal membrane is an active process is demonstrated by several important experimental observations:

1. Transport of most of them, especially glucose and galactose, can be blocked by metabolic inhibitors, such as iodoacetic acid, cyanides, and phlorhizin.

2. The transport is selective, specifically transporting certain monosaccharides without transporting others. The order of preference for transporting different monosaccharides and their relative rates of transport in comparison with glucose are:

3. There is a maximum rate of transport for each type of monosaccharide. The most rapidly transported monosaccharide is galactose, with glucose running a close second. Fructose, which is also one of the three important monosaccharides for nutrition, is absorbed less than half as rapidly as either galactose or glucose; also, its mechanism of absorption is different, as will be explained below.

4. There is competition between certain sugars for the respective carrier system. For instance, if large amounts of galactose are being transported, the amount of glucose that can be transported simultaneously is considerably reduced.

Mechanism of Glucose and Galactose Absorption. Glucose and galactose transport either ceases or is greatly reduced wherever active sodium transport is blocked. Therefore, it is assumed that the energy required for transport of these two monosaccharides is actually provided by the sodium transport system. A theory that attempts to explain this is the following: It is known that the carrier protein for transport of glucose (which is the carrier for galactose as well) is present in the brush border of the epithelial cell. However, this carrier will not transport the glucose in the absence of sodium transport. Therefore, it is believed that the carrier protein has receptor sites for both a glucose molecule and a sodium ion, and that it will not transport either of these to the interior of the epithelial cell until both receptor sites are simultaneously filled. The energy to cause movement of the carrier from the exterior of the membrane to the interior is derived from the difference in sodium concentration between the outside and inside. That is, as sodium diffuses to the inside of the cell it „drags“ the glucose along with it, thus providing the energy for transport of the glucose. For obvious reasons, this explanation is called the sodium cotransport theory for glucose transport; it is also called secondary active transport of glucose. This sodium cotransport of glucose obviously moves the glucose only to the interior of the cell. However, this increases the intracellular glucose concentration to a higher thaormal level, and the glucose then diffuses, probably by facilitated diffusion, through the basolateral membrane of the epithelial cell into the extracellular fluid.

Subsequently, we will see that sodium transport is also required for transport of many if not all amino acids, suggesting a similar „carrier-drag“ mechanism for ammo acid transport.

Absorption of Fructose. Transport of fructose is slightly different from that of most other monosaccharides. It is not blocked by some of the same metabolic poisons – specifically, phlorhizin – and it does not require metabolic energy for transport, even though it does require a specific carrier. Therefore, it is transported by facilitated diffusion rather than active transport. Also, it is mainly converted into glucose inside the epithelial cell before entering the portal blood, the fructose first becoming phosphorylated, then converted to glucose, and finally released from the epithelial cell into the blood.

 

Products of fats hydrolyses

 

As fats are digested to form monoglycerides and free fatty acids, both of these digestive end-products become dissolved in the lipid portion of the bile acid micelles. Because of the molecular dimensions of these micelles, only 2,5 nanometers in diameter, and also because of their highly charged exterior, they are soluble in the chyme. In this form the monoglycerides and the fatty acids are transported to the surfaces of the brush border microvilli, even penetrating into the recesses among the moving, agitating microvilli. On coming in contact with these surfaces, both the monoglycerides and the fatty acids immediately diffuse through the epithelial membrane, because they are equally as soluble in this membrane as in the micelles. This leaves the bile acid micelles still in the chyme. The micelles then diffuse back through the chyme and absorb still more monoglycerides and fatty acids, and similarly transport these also to the epithelial cells. Thus, the bile acids perform a „ferrying“ function, which is highly important for fat absorption. In the presence of an abundance of bile acids, approximately 97 per cent of the fat is absorbed; in the absence of bile acids, only 50 to 60 per cent is normally absorbed.

The mechanism for absorption of the monoglycerides and fatty acids through the brush border is based entirely on the fact that both these substances are highly lipid-soluble. Therefore, they become dissolved in the membrane and simply diffuse to the interior of the cell.

The undigested triglycerides and the diglycerides are both also highly soluble in the lipid membrane of the epithelial cell. However, only small quantities of these are normally absorbed because the bile acid micelles will not dissolve either triglycerides or diglycerides and therefore will not ferry them to the epithelial membrane.

After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the smooth endoplasmic reticulum, and here they are mainly recombined to form new triglycerides. However, a few of the monoglycerides are further digested into glycerol and fatty acids by an epithelial cell lipase. Then, the free fatty acids are reconstituted by the smooth endoplasmic reticulum into triglycerides. Most of the glycerol that is utilized for this purpose is synthesized de novo from alpha-glycerophosphate, this synthesis requiring both energy from ATP and a complex of enzymes to catalyze the reactions.

Once formed, the triglycerides aggregate within the endoplasmic reticulum into globules along with absorbed cholesterol, absorbed phospholipids, and small amounts of newly synthesized cholesterol and phospholipids. The phospholipids arrange themselves in these globules with the fatty portion of the phospholipid toward the center and the polar portions located on the surface. This provides an electrically charged surface that makes these globules miscible with the fluids of the cell. In addition, small amounts of beta-lipoprotein, also synthesized by the endoplasmic reticulum, coat part of the surface of each globule. In this form the globule diffuses to the side of the epithelial cell and is excreted by the process of cellular exocytosis into the space between the cells; from there it passes into the lymph in the central lacteal of the villus. These globules are then called chylomicrons.

The beta-lipoprotein is essential for cellular exocytosis of the chylomicrons to occur, because this protein provides a means for attaching the fatty globule to the cell membrane before it is extruded. In persons who have a genetic inability to form this (3-lipoprotein, the epithelial cells become engorged with fatty products that cannot proceed the rest of the way to be absorbed.

Transport of the Chylomicrons in the Lymph. From the sides of the epithelial cells the chylomicrons wend their way into the central lacteals of the villi and from here are propelled, along with the lymph, by the lymphatic pump upward through the thoracic duct to be emptied into the great veins of the neck. Between 80 and 90 per cent of all fat absorbed from the gut is absorbed in this manner and is transported to the blood by way of the thoracic lymph in the form of chylomicrons.

Direct Absorption of Fatty Acids into the Portal Blood. Small quantities of short chain fatty acids, such as those from butterfat, are absorbed directly into the portal blood rather than being converted into triglycerides and absorbed into the lymphatics. The cause of this difference between short and long chain fatty acid absorption is that the shorter chain fatty acids are more water-soluble and are not reconverted into triglycerides by the endoplasmic reticulum. This allows direct diffusion of these fatty acids from the epithelial cells into the capillary blood of the villus.

TEMPERATURE REGULATION

 

The human body has the remarkable capacity for regulating its core temperature somewhere between 98°F and 100°F when the ambient temperature is between approximately 68°F and 130°F according to Guyton. This presumes a nude body and dry air.

The external heat transfer mechanisms are radiation, conduction and convection and evaporation of perspiration. The process is far more than the passive operation of these heat transfer mechanisms, however. The body takes a very active role in temperature regulation.

The temperature of the body is regulated by neural feedback mechanisms which operate primarily through the hypothalmus. The hypothalmus contains not only the control mechanisms, but also the key temperature sensors. Under control of these mechanisms, sweating begins almost precisely at a skin temperature of 37°C and increases rapidly as the skin temperature rises above this value. The heat production of the body under these conditions remains almost constant as the skin temperature rises. If the skin temperature drops below 37°C a variety of responses are initiated to conserve the heat in the body and to increase heat production. These include

·          Vasoconstriction to decrease the flow of heat to the skin.

·          Cessation of sweating.

·          Shivering to increase heat production in the muscles.

·          Secretion of norepinephrine, epinephrine, and thyroxine to increase heat production

·          In lower animals, the erection of the hairs and fur to increase insulation.

Age Factors Very young and very old people are limited in their ability to regulate body temperature when exposed to environmental extremes. A newborn infant’s body temperature decreases if the infant is exposed to a cool environment for a long period. Elderly people also are not able to produce enough heat to maintain body temperature in a cool environment. With regard to overheating in these age groups, heat loss mechanisms are not fully developed in the newborn. The elderly do not lose as much heat from their skin as do younger people. Both groups should be protected from extreme temperatures.

Normal Body Temperature The normal temperature range obtained by either a mercury or an electronic thermometer may extend from 36.2°C to 37.6°C (97°F to 100°F). Body temperature varies with the time of day. Usually, it is lowest in the early morning because the muscles have been relaxed and no food has been taken in for several hours. Temperature tends to be higher in the late afternoon and evening because of physical activity and consumption of food. Normal temperature also varies in different parts of the body. Skin temperature obtained in the axilla (armpit) is lower than mouth temperature, and mouth temperature is a degree or so lower than rectal temperature. It is believed that, if it were possible to place a thermometer inside the liver, it would register a degree or more higher than rectal temperature. The temperature within a muscle might be even higher during activity. Although the Fahrenheit scale is used in the United States, in most parts of the world, temperature is measured with the Celsius thermometer. On this scale, the ice point is at 0° and the normal boiling point of water is at 100°, the interval between these two points being divided into 100 equal units. The Celsius scale is also called the centigrade scale (think of 100 cents in a dollar).

Fever

Fever is a condition in which the body temperature is higher than normal. An individual with a fever is described as febrile. Usually, the presence of fever is due to an infection, but there can be many other causes, such as malignancies, brain injuries, toxic reactions, reactions to vaccines, and diseases involving the central nervous system (CNS). Sometimes, emotional upsets can bring on a fever. Whatever the cause, the effect is to reset the body’s thermostat in the hypothalamus. Curiously enough, fever usually is preceded by a chill—that is, a violent attack of shivering and a sensation of cold that blankets and heating pads seem unable to relieve. As a result of these reactions, heat is generated and stored, and when the chill subsides, the body temperature is elevated. The old adage that a fever should be starved is completely wrong. During a fever, there is an increase in metabolism that is usually proportional to the degree of fever. The body uses available sugars and fats, and there is an increase in the use of protein. During the first week or so of a fever, there is definite evidence of protein destruction, so a high-calorie diet with plenty of protein is recommended. When a fever ends, sometimes the drop in temperature to normal occurs very rapidly. This sudden fall in temperature is called the crisis, and it is usually accompanied by symptoms indicating rapid heat loss: profuse perspiration, muscular relaxation, and dilation of blood vessels in the skin. A gradual drop in temperature, in contrast, is known as lysis. A drug that reduces fever is described as antipyretic. The mechanism of fever production is not completely understood, but we might think of the hypothalamus as a thermostat that is set higher during fever thaormally. This change in the heat-regulating mechanism often follows the injection of a foreign protein or the entrance into the bloodstream of bacteria or their toxins. Substances that produce fever are called pyrogens. Up to a point, fever may be beneficial because it steps up phagocytosis (the process by which white blood cells destroy bacteria and other foreign material), inhibits the growth of certain organisms, and increases cellular metabolism, which may help recovery from disease.

 

In the body, heat is produced by muscular exercise, assimilation of food, and all the vital processes that contribute to the basal metabolic rate. It is lost from the body by radiation, conduction, and vaporization of water in the respiratory passages and on the skin. Small amounts of heat are also removed in the urine and feces. The balance between heat production and heat loss determines the body temperature. Because the speed of chemical reactions varies with the temperature and because the enzyme systems of the body have narrow temperature ranges in which their function is optimal, normal body function depends upon a relatively constant body temperature.

 

Invertebrates generally cannot adjust their body temperatures and so are at the mercy of the environment. In vertebrates, mechanisms for maintaining body temperature by adjusting heat production and heat loss have evolved. In reptiles, amphibia, and fish, the adjusting mechanisms are relatively rudimentary, and these species are called “cold-blooded” (poikilothermic) because their body temperature fluctuates over a considerable range. In birds and mammals, the ”warm-blooded” (homeothermic) animals, a group of reflex responses that are primarily integrated in the hypothalamus operate to maintain body temperature within a narrow range in spite of wide fluctuations in environmental temperature. The hibernating mammals are a partial exception. While awake, they are homeothermic, but during hibernation, their body temperature falls.

Normal Body Temperature

In homeothermic animals, the actual temperature at which the body is maintained varies from species to species and, to a lesser degree, from individual to individual. In humans, the traditional normal value for the oral temperature is 37 °C (98.6 °F), but in one large series of normal young adults, the morning oral temperature averaged 36.7 °C, with a standard deviation of 0.2 °C.

 

Heat Production

A variety of basic chemical reactions contribute to body heat production at all times. Ingestion of food increases heat production because of the specific dynamic action of the food, but the major source of heat is the contraction of skeletal muscle. Heat production can be varied by endocrine mechanisms in the absence of food intake or muscular exertion. Epinephrine and norepinephrine produce a rapid but short-lived increase in heat production; thyroid hormones produce a slowly developing but prolonged increase, Furthermore, sympathetic discharge is decreased during fasting and increased by feeding.

 

Heat Loss

Radiation is the transfer of heat from one object to another with which it is not in contact.

 Conduction is heat exchange between objects at different temperatures that are in contact with one another. The amount of heat transferred by conduction is proportionate to the temperature difference between the 2 objects (thermal gradient).

Convection, the movement of the molecules O₂ a gas or a liquid at one temperature to another location that is at a different temperature, aids conduction. When an individual is in a cold environment, heat is lost by conduction to the surrounding air and by radiation to cool objects in the vicinity. In a hot environment, heat is transferred to the individual by these processes and adds to the heat load.

Thus, in a sense, radiation and conduction work against the maintenance of body temperature. On a cold but sunny day, the heat of the sun reflected off bright objects exerts an appreciable warming effect. It is the heat reflected from the snow, for example, that makes it possible to ski in fairly light clothes even though the air temperature is below freezing.

Since conduction occurs from the surface of one object to the surface of another, the temperature of the skin determines to a large extent the degree to which body heat is lost or gained. The amount of heat reaching the skin from the deep tissues can be varied by changing the blood flow to the skin. When the cutaneous vessels are dilated, warm blood wells up into the skin, whereas in the maximally vasoconstricted state, heat is held centrally in the body. The rate at which heat is transferred from the deep tissues to the skin is called the tissue conductance. Birds have a layer of feathers next to the skin, and most mammals have a significant layer of hair or fur. Heat is conducted from the skin to the air trapped in this layer and from the trapped air to the exterior. When the thickness of the trapped layer is increased by fluffing the feathers or erection of the hairs (horripilation), heat transfer across the layer is reduced and heat losses (or, in a hot environment, heat gains) are decreased. “Goose pimples ” are the result of horripilation in humans; they are the visible manifestation of cold-induced contraction of the piloerector muscles attached to the rather meager hair supply. Humans usually supplement this layer of hair with a layer of clothes. Heat is conducted from the skin to the layer of air trapped by the clothes, from the inside of the clothes to the outside, and from the outside of the clothes to the exterior. The magnitude of the heat transfer across the clothing, a function of its texture and thickness, is the most important determinant of how warm or cool the clothes feel, but other factors, especially the size of the trapped layer of warm air, are important also. Dark clothes absorb radiated heat, and light-colored clothes reflect it back to the exterior.

 

The other major process transferring heat from the body in humans and those animals that sweat is vaporization of water on the skin and mucous membranes of the mouth and respiratory passages.

Vaporization of 1 g of water removes about 0.6 kcal of heat. A certain amount of water is vaporized at all times. This insensible water loss amounts to 50 mL/h in humans. When sweat secretion is increased, the degree to which the sweat vaporizes depends upon the humidity of the environment. It is common knowledge that one feels hotter on a humid day. This is due in part to the decreased vaporization of sweat, but even under conditions in which vaporization of sweat is complete, an individual in a humid environment feels warmer than an individual in a dry environment. The reason for this difference is not known, but it seems related to the fact that in the humid environment sweat spreads over a greater area of skin before it evaporates.

Endothermic evaporation cools body

a. Sweat glands secrete sweat continuously

b. Body temperature increase

 

 Blood vessels dilate

 Sweat glands stimulated

During muscular exertion in a hot environment, sweat secretion reaches values as high as 1600 mL/h, and in a dry atmosphere, most of this sweat is vaporized. Heat loss by vaporization of water therefore varies from 30 to over 900 kcal/h.

Some mammals lose heat by panting. This rapid, shallow breathing greatly increases the amount of water vaporized in the mouth and respiratory passages and therefore the amount of heat lost. Because the breathing is shallow, it produces relatively little change in the composition of alveolar air.

The relative contribution of each of the processes that transfer heat away from the body varies with the environmental temperature. At 21 °C, vaporization is a minor component in humans at rest. As the environmental temperature approaches body temperature, radiation losses decline and vaporization losses increase.

Temperature-Regulating Mechanisms

The reflex and semireflex thermoregulatory includes autonomic, somatic, endocrine, and behavioral changes. One group of responses increases heat loss and decreases heat production; the other decreases heat loss and increases heal production. In general, exposure to heat stimulates the former group of responses and inhibits the latter, whereas exposure to cold does the opposite.

Curling up “in a ball” is a common reaction to cold in animals and has a counterpart in the position some people assume on climbing into a cold bed. Curling up decreases the body surface exposed to the environment. Shivering is an involuntary response of the skeletal muscles, but cold also causes a semiconscious general increase in motor activity. Examples include foot stamping and dancing up and down on a cold day. Increased catecholamine secretion is an important endocrine response to cold; adrenal medullectomized rats die faster thaormal controls when exposed to cold. TSH secretion is increased by cold and decreased by heat in laboratory animals, but the change in TSH secretion produced by cold in adult humans is small and of questionable significance. It is common knowledge that activity is decreased in hot weather – the “it’s too hot to move” reaction.

Then no regulatory adjustments involve local responses and more general reflex responses. When cutaneous blood vessels are cooled, they become more sensitive to catecholamines and the arterioles and venules constrict. This local effect of cold directs blood away from the skin and into the venae comitantes, the deep veins that run alongside the arteries. Heat is transferred from the arterial to the venous blood and carried back into the body without reaching the skin (counter current exchange).

The reflex responses activated by cold are controlled from the posterior hypothalamus. Those activated by warmth are primarily controlled from the anterior hypothalamus, although some thermoregulation against heat still occurs after decerebration at the level of the rostral midbrain. Stimulation of the anterior hypothalamus causes cutaneous vasodilatation and sweating, and lesions in this region cause hyperthermia, with rectal temperatures sometimes reaching 43 °C (109.4 °F). Posterior hypothalamic stimulation causes shivering, and the body temperature of animals with posterior hypothalamic lesions falls toward that of the environment.

There is some evidence that in primates and humans serotonin is a synaptic mediator in the centers controlling the mechanisms activated by cold, and norepinephrine plays a similar role in those activated by heat. However, there are marked species variations in the temperature responses to these amines. Peptides may also be involved, but the details of the central synaptic connections concerned with thermoregulation are still unknown.

The Role of the Hypothalamus Many areas of the body take part in heat regulation, but the most important center is the hypothalamus, the area of the brain located just above the pituitary gland. Some of the cells in the hypothalamus control heat production in body tissues, whereas another group of cells controls heat loss. Regulation is based on the temperature of the blood circulating through the brain and also on input from temperature receptors in the skin. If these two factors indicate that too much heat is being lost, impulses are sent quickly from the hypothalamus to the autonomic (involuntary) nervous system, which in turn causes constriction of the skin blood vessels to reduce heat loss. Other impulses are sent to the muscles to cause shivering, a rhythmic contraction of many muscles, which results in increased heat production. Furthermore, the output of epinephrine may be increased if necessary. Epinephrine increases cell metabolism for a short period, and this in turn increases heat production.

If there is danger of overheating, the hypothalamus stimulates the sweat glands to increase their activity. Impulses from the hypothalamus also cause blood vessels in the skin to dilate, so that increased blood flow to the skin will result in greater heat loss. The hypothalamus may also promote muscle relaxation to minimize heat production. Muscles are especially important in temperature regulation because variations in the activity of these large tissue masses can readily increase or decrease heat generation. Because muscles form roughly one-third of the body, either an involuntary or an intentional increase in their activity can form enough heat to offset a considerable decrease in the temperature of the environment.

Renal physiology (Latin rēnēs, “kidney”) is the study of the physiology of the kidney. This encompasses all functions of the kidney, including reabsorption of glucose, amino acids, and other small molecules; regulation of sodium, potassium, and other electrolytes; regulation of fluid balance and blood pressure; maintenance of acid-base balance; the production of various hormones including erythropoietin, and the activation of vitamin D

Much of renal physiology is studied at the level of the nephron, the smallest functional unit of the kidney. Each nephron begins with a filtration component that filters blood entering the kidney. This filtrate then flows along the length of the nephron, which is a tubular structure lined by a single layer of specialized cells and surrounded by capillaries. The major functions of these lining cells are the reabsorption of water and small molecules from the filtrate into the blood, and the secretion of wastes from the blood into the urine.

This illustration demonstrates the normal kidney physiology. It also includes illustrations showing where some types of diuretics act, and what they do.

Proper function of the kidney requires that it receives and adequately filters blood. This is performed at the microscopic level by many hundreds of thousands of filtration units called renal corpuscles, each of which is composed of a glomerulus and a Bowman’s capsule. A global assessment of renal function is often ascertained by estimating the rate of filtration, called the glomerular filtration rate (GFR).

Functions of the kidney

The functions of the kidney can be divided into three groups: secretion of hormones, gluconeogenesis and extracellular homeostasis of pH and blood components. The nephron is the functional unit of the kidney.

Secretion of hormones

Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.

Secretion of renin, which is a key part of the renin-angiotensin-aldosterone system.

Secretion of the active form of vitamin D (calcitriol) and prostaglandins.

Gluconeogenesis

The kidney in humans is capable of producing glucose from lactate, glycerol and glutamine. The kidney is responsible for about half of the total gluconeogenesis in fasting humans. The regulation of glucose production in the kidney is achieved by action of insulin, catecholamines and other hormones. Renal gluconeogenesis takes place in the renal cortex. The renal medulla is incapable of producing glucose due to absence of necessary enzymes.

The body is very sensitive to its pH. Outside the range of pH that is compatible with life, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself. The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. Acids are divided into “volatile acids” and “nonvolatile acids”. See also titratable acid.

The major homeostatic control point for maintaining this stable balance is renal excretion. The kidney is directed to excrete or retain sodium via the action of aldosterone, antidiuretic hormone (ADH, or vasopressin), atrial natriuretic peptide (ANP), and other hormones. Abnormal ranges of the fractional excretion of sodium can imply acute tubular necrosis or glomerular dysfunction.

Mechanisms

 Diagram showing the basic physiologic mechanisms of the kidney

The kidney’s ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion, whose sum is renal excretion.

Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate

Filtration

The blood is filtered by nephrons, the functional units of the kidney. Each nephron begins in a renal corpuscle, which is composed of a glomerulus enclosed in a Bowman’s capsule. Cells, proteins, and other large molecules are filtered out of the glomerulus by a process of ultrafiltration, leaving an ultrafiltrate that resembles plasma (except that the ultrafiltrate has negligible plasma proteins) to enter Bowman’s space. Filtration is driven by Starling forces.

 

The ultrafiltrate is passed through, in turn, the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and a series of collecting ducts to form urine.

 

Reabsorption

Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) because these substances have already been absorbed once (particularly in the intestines).

Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport.

Secretion

Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport.

Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons.

Many drugs are eliminated by tubular secretion. Further reading: Table of medication secreted in kidney

Measurement of renal function

A simple means of estimating renal function is to measure pH, blood urea nitrogen, creatinine, and basic electrolytes (including sodium, potassium, chloride, and bicarbonate). As the kidney is the most important organ in controlling these values, any derangement in these values could suggest renal impairment.

There are several more formal tests and ratios involved in estimating renal function:

Renal blood flow

From Wikipedia, the free encyclopedia

  (Redirected from Renal plasma flow)

 Jump to: navigation, search Parameter    Value

renal blood flow  RBF=1000 ml/min

hematocrit  HCT=40%

renal plasma flow         RPF=600 ml/min

filtration fraction FF=20%

glomerular filtration rate        GFR=120 ml/min

urine flow rate     V=1 mL/min

Sodium       Inulin          Creatinine   PAH

SNa=150 mEq/L  SIn=1 mg/mL       SCr=0.01 mg/ml  SPAH=

UNa=710 mEq/L UIn=150 mg/mL  UCr=1.25 mg/mL          UPAH=

CNa=5 mL/min    CIn=150 ml/min  CCr=125 mL/min          CPAH=420 ml/min

                            ER=90%

                            ERPF=540 ml/min

In the physiology of the kidney, renal blood flow (RBF) is the volume of blood delivered to the kidneys per unit time. In humans, the kidneys together receive roughly 22% of cardiac output, amounting to 1.1 L/min in a 70-kg adult male. RBF is closely related to renal plasma flow (RPF), which is the volume of blood plasma delivered to the kidneys per unit time.

While the terms generally apply to arterial blood delivered to the kidneys, both RBF and RPF can be used to quantify the volume of venous blood exiting the kidneys per unit time. In this context, the terms are commonly given subscripts to refer to arterial or venous blood or plasma flow, as in RBFa, RBFv, RPFa, and RPFv. Physiologically, however, the differences in these values are negligible so that arterial flow and venous flow are often assumed equal.

In anatomy, urinary system, the kidneys filter wastes (such as urea) from the blood and excrete them, along with water, as urine. The medical field that studies the kidneys and diseases of the kidney is called nephrology (nephro- meaning kidney is from the Ancient Greek word nephros; the adjective renal meaning related to the kidney is from Latin rēnēs, meaning kidneys).

 

In humans, the kidneys are located in the posterior part of the abdomen. There is one on each side of the spine; the right kidney sits just below the liver, the left below the diaphragm and adjacent to the spleen. Above each kidney is an adrenal gland (also called the suprarenal gland). The asymmetry within the abdominal cavity caused by the liver results in the right kidney being slightly lower than the left one while the left kidney is located slightly more medial.

The kidneys are retroperitoneal, which means they lie behind the peritoneum, the lining of the abdominal cavity. They are approximately at the vertebral level T12 to L3. The upper parts of the kidneys are partially protected by the eleventh and twelfth ribs, and each whole kidney is surrounded by two layers of fat (the perirenal and pararenal fat) which help to cushion it. Congenital absence of one or both kidneys, known as unilateral or bilateral renal agenesis can occur.

Organization

Above each human kidney is one of the two adrenal glands.

In a normal human adult, each kidney is about 10 cm long, 5.5 cm in width and about 3 cm thick, weighing 150 grams. Together, kidneys weigh about 0.5% of a person’s total body weight. The kidneys are “bean-shaped” organs, and have a concave side facing inwards (medially). On this medial aspect of each kidney is an opening, called the hilum, which admits the renal artery, the renal vein, nerves, and the ureter.

The outer portion of the kidney is called the renal cortex, which sits directly beneath the kidney’s loose connective tissue/fibrous capsule. Deep to the cortex lies the renal medulla, which is divided into 10-20 renal pyramids in humans. Each pyramid together with the associated overlying cortex forms a renal lobe. The tip of each pyramid (called a papilla) empties into a calyx, and the calices empty into the renal pelvis. The pelvis transmits urine to the urinary bladder via the ureter.

Blood supply

Each kidney receives its blood supply from the renal artery, two of which branch from the abdominal aorta. Upon entering the hilum of the kidney, the renal artery divides into smaller interlobar arteries situated between the renal papillae. At the outer medulla, the interlobar arteries branch into arcuate arteries, which course along the border between the renal medulla and cortex, giving off still smaller branches, the cortical radial arteries (sometimes called interlobular arteries). Branching off these cortical arteries are the afferent arterioles supplying the glomerular capillaries, which drain into efferent arterioles. Efferent arterioles divide into peritubular capillaries that provide an extensive blood supply to the cortex. Blood from these capillaries collects in renal venules and leaves the kidney via the renal vein. Efferent arterioles of glomeruli closest to the medulla (those that belong to juxtamedullary nephrons) send branches into the medulla, forming the vasa recta. Blood supply is intimately linked to blood pressure.

Nephron

Parts of the kidney: 1. Renal pyramid

The basic functional unit of the kidney is the nephron, of which there are more than a million within the cortex and medulla of each normal adult human kidney. Nephrons regulate water and solute within the cortex and medulla of each normal adult human kidney. Nephrons regulate water and soluble matter (especially electrolytes) in the body by first filtering the blood under pressure, and then reabsorbing some necessary fluid and molecules back into the blood while secreting other, unneeded molecules. Reabsorption and secretion are accomplished with both cotransport and countertransport mechanisms established in the nephrons and associated collecting ducts.

Collecting duct system

The fluid flows from the nephron into the collecting duct system. This segment of the nephron is crucial to the process of water conservation by the organism. In the presence of antidiuretic hormone (ADH; also called vasopressin), these ducts become permeable to water and facilitate its reabsorption, thus concentrating the urine and reducing its volume. Conversely, when the organism must eliminate excess water, such as after excess fluid drinking, the production of ADH is decreased and the collecting tubule becomes less permeable to water, rendering urine dilute and abundant. Failure of the organism to decrease ADH production appropriately, a condition known as syndrome of inappropriate ADH (SIADH), may lead to water retention and dangerous dilution of body fluids, which in turn may cause severe neurological damage. Failure to produce ADH (or inability of the collecting ducts to respond to it) may cause excessive urination, called diabetes insipidus (DI).

A second major function of the collecting duct system is the maintenance of acid-base homeostasis.

After being processed along the collecting tubules and ducts, the fluid, now called urine, is drained into the bladder via the ureter, to be finally excluded from the organism.

Excretion of waste products

The kidneys excrete a variety of waste products produced by metabolism, including the nitrogenous wastes: urea (from protein catabolism) and uric acid (from nucleic acid metabolism).

Homeostasis

The kidney is one of the major organs involved in whole-body homeostasis. Among its homeostatic functions are acid-base balance, regulation of electrolyte concentrations, control of blood volume, and regulation of blood pressure. The kidneys accomplish these homeostatic functions independently and through coordination with other organs, particularly those of the endocrine system. The kidney communicates with these organs through hormones secreted into the bloodstream.

 

Acid-base balance

The kidneys regulate the pH, by eliminating H ions concentration called augmentation mineral ion concentration, and water composition of the blood.

By exchanging hydronium ions and hydroxyl ions, the blood plasma is maintained by the kidney at a slightly alkaline pH of 7.4. Urine, on the other hand, is acidic at pH 5 or alkaline at pH 8.

The pH is maintained through four main protein transporters: NHE3 (a sodium–hydrogen exchanger), V-type H-ATPase (an isoform of the hydrogen ATPase), NBC1 (a sodium-bicarbonate cotransporter) and AE1 (an anion exchanger which exchanges chloride for bicarbonate). Due to the polar alignment of cells in the renal epithelia NHE3 and the H-ATPase are exposed to the lumen (which is essentially outside the body), on the apical side of the cells, and are responsible for excreting hydrogen ions (or protons). Conversely, NBC1 and AE1 are on the basolateral side of the cells, and allow bicarbonate ions to move back into the extracellular fluid and thus are returned to the blood plasma.

Acid–base homeostasis is the part of human homeostasis concerning the proper balance between acids and bases, also called body pH. The body is very sensitive to its pH level, so strong mechanisms exist to maintain it. Outside the acceptable range of pH, proteins are denatured and digested, enzymes lose their ability to function, and death may occur.

 

Acids and bases

Acid–base imbalance occurs when a significant insult causes the blood pH to shift out of the normal range (7.35 to 7.45). In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.18 to 7.38). An excess of acid in the blood is called acidemia and an excess of base is called alkalemia. The process that causes the imbalance is classified based on the etiology of the disturbance (respiratory or metabolic) and the direction of change in pH (acidosis or alkalosis). There are four basic processes: metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. One or a combination may occur at any given time.

 

Blood pressure

Sodium ions are controlled in a homeostatic process involving aldosterone which increases sodium ion absorption in the distal convoluted tubules.

When blood pressure becomes low, a proteolytic enzyme called Renin is secreted by cells of the juxtaglomerular apparatus (part of the distal convoluted tubule) which are sensitive to pressure. Renin acts on a blood protein, angiotensinogen, converting it to angiotensin I (10 amino acids). Angiotensin I is then converted by the Angiotensin-converting enzyme (ACE) in the lung capillaries to Angiotensin II (8 amino acids), which stimulates the secretion of Aldosterone by the adrenal cortex, which then affects the kidney tubules.

Aldosterone stimulates an increase in the reabsorption of sodium ions from the kidney tubules which causes an increase in the volume of water that is reabsorbed from the tubule. This increase in water reabsorption increases the volume of blood which ultimately raises the blood pressure.

Plasma volume

Any significant rise or drop in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. A rise in osmolality causes the gland to secrete antidiuretic hormone, resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.

Hormone secretion

The kidneys secrete a variety of hormones, including erythropoietin, urodilatin, renin and vitamin D.

Secretion of hormones

Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.

Secretion of renin, which is a key part of the renin-angiotensin-aldosterone system.

Secretion of the active form of vitamin D (calcitriol) and prostaglandins.

Erythropoietin, also known as erythropoetin or erthropoyetin (/ɨˌrɪθrɵˈpɔɪ.ɨtɨn/, /ɨˌrɪθrɵˈpɔɪtən/, and /ɨˌriːθrɵ-/) or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine (protein signaling molecule) for erythrocyte (red blood cell) precursors in the bone marrow. Human EPO has a molecular weight of 34 kDa.

Also called hematopoietin or hemopoietin, it is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and tubular epithelial tubule. It is also produced in perisinusoidal cells in the liver. While liver production predominates in the fetal and perinatal period, renal production is predominant during adulthood. In addition to erythropoiesis, erythropoietin also has other known biological functions. For example, it plays an important role in the brain’s response to neuronal injury. EPO is also involved in the wound healing process.

When exogenous EPO is used as a performance-enhancing drug, it is classified as an erythropoiesis-stimulating agent (ESA). Exogenous EPO can often be detected in blood, due to slight differences from the endogenous protein, for example, in features of posttranslational modification.

 

Erythropoietin

Function

Primary role in red blood cell production

Erythropoietin is an essential hormone for red cell production. Without it, definitive erythropoiesis does not take place. Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation. Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in humans) by promoting their survival through protecting these cells from apoptosis.

Erythropoietin is the primary erythropoietic factor that cooperates with various other growth factors (e.g., IL-3, IL-6, glucocorticoids, and SCF) involved in the development of erythroid lineage from multipotent progenitors. The burst-forming unit-erythroid (BFU-E) cells start erythropoietin receptor expression and are sensitive to erythropoietin. Subsequent stage, the colony-forming unit-erythroid (CFU-E), expresses maximal erythropoietin receptor density and is completely dependent on erythropoietin for further differentiation. Precursors of red cells, the proerythroblasts and basophilic erythroblasts also express erythropoietin receptor and are therefore affected by it.

Additional nonhematopoietic roles

Erythropoietin has a range of actions including vasoconstriction-dependent hypertension, stimulating angiogenesis, and inducing proliferation of smooth muscle fibers. It can increase iron absorption by suppressing the hormone hepcidin.

EPO also affects neuronal protection during hypoxic conditions (stroke, etc.). Trials on human subjects are not yet reported; if proven to be a viable treatment of heart attack and stroke patients, it could improve the outcome and quality of life. The reasoning behind such a proposal is that EPO levels of 100 times the baseline have been detected in brain tissue as a natural response to (primarily) hypoxic damage.

Multiple studies have suggested that EPO improves memory. This effect is independent of its effect on hematocrit. Rather, it is associated with an increase in hippocampal response and effects on synaptic connectivity, neuronal plasticity, and memory-related neural networks.EPO may also be an effective treatment for depression.

Mechanism of action

Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR).

EPO is highly glycosylated (40% of total molecular weight), with half-life in blood around five hours. EPO’s half-life may vary between endogenous and various recombinant versions. Additional glycosylation or other alterations of EPO via recombinant technology have led to the increase of EPO’s stability in blood (thus requiring less frequent injections). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signaling cascade. Erythropoietin receptor expression is found in a number of tissues, such as bone marrow and peripheral/central nervous tissue. In the bloodstream, red cells themselves do not express erythropoietin receptor, so cannot respond to EPO. However, indirect dependence of red cell longevity in the blood on plasma erythropoietin levels has been reported, a process termed neocytolysis.

Synthesis and regulation

Erythropoietin levels in blood are quite low in the absence of anemia, at around 10 mU/ml. However, in hypoxic stress, EPO production may increase a 1000-fold, reaching 10,000 mU/ml of blood. EPO is produced mainly by peritubular capillary lining cells of the renal cortex, which are highly specialized, epithelial-like cells. It is synthesized by renal peritubular cells in adults, with a small amount being produced in the liver.Regulation is believed to rely on a feedback mechanism measuring blood oxygenation. Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and proteosomally digested in the presence of oxygen.

Medical uses

Main article: Epoetin alfa

Erythropoietins available for use as therapeutic agents are produced by recombinant DNA technology in cell culture, and include Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); they are used in treating anemia resulting from chronic kidney disease, inflammatory bowel disease (Crohn’s disease and ulcer colitis) and myelodysplasia from the treatment of cancer (chemotherapy and radiation), but include boxed warnings of increased risk of death, myocardial infarction, stroke, venous thromboembolism, tumor recurrence, and other severe off-target effects.

 Also known as an angiotensinogenase, is an enzyme that participates in the body’s renin-angiotensin system (RAS)—also known as the renin-angiotensin-aldosterone axis—that mediates extracellular volume (i.e., that of the blood plasma, lymph and interstitial fluid), and arterial vasoconstriction. Thus, it regulates the body’s mean arterial blood pressure.

Renin

Renin-angiotensin system

 The renin-angiotensin system, showing role of renin at bottom.

The renin enzyme circulates in the blood stream and breaks down (hydrolyzes) angiotensinogen secreted from the liver into the peptide angiotensin I.

Angiotensin I is further cleaved in the lungs by endothelial-bound angiotensin-converting enzyme (ACE) into angiotensin II, the most vasoactive peptide.[4][5] Angiotensin II is a potent constrictor of all blood vessels. It acts on the smooth muscle and, therefore, raises the resistance posed by these arteries to the heart. The heart, trying to overcome this increase in its ‘load’, works more vigorously, causing the blood pressure to rise. Angiotensin II also acts on the adrenal glands and releases Aldosterone, which stimulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to increase re-absorption of sodium and water, leading to raised blood volume and raised blood pressure. The RAS also acts on the CNS to increase water intake by stimulating thirst, as well as conserving blood volume, by reducing urinary loss through the secretion of Vasopressin from the posterior pituitary gland.

The normal concentration of renin in adult human plasma is 1.98-24.6 ng/L in the upright position.

Function

Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into angiotensin II by ACE, the angiotensin-converting enzyme primarily within the capillaries of the lungs. Angiotensin II then constricts blood vessels, increases the secretion of ADH and aldosterone, and stimulates the hypothalamus to activate the thirst reflex, each leading to an increase in blood pressure.

Renin is secreted from kidney cells, which are activated via signaling from the macula densa, which responds to the rate of fluid flow through the distal tubule, by decreases in renal perfusion pressure (through stretch receptors in the vascular wall), and by sympathetic nervous stimulation, mainly through beta-1 adrenoceptor activation. A drop in the rate of flow past the macula densa implies a drop in renal filtration pressure. Renin’s primary function is therefore to eventually cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.

Renin can bind to ATP6AP2, which results in a fourfold increase in the conversion of angiotensinogen to angiotensin I over that shown by soluble renin. In addition, renin binding results in phosphorylation of serine and tyrosine residues of ATP6AP2.

The level of renin mRNA appears to be modulated by the binding of HADHB, HuR and CP1 to a regulatory region in the 3′ UTR.

Genetics

The gene for renin, REN, spans 12 kb of DNA and contains 8 introns.It produces several mRNA that encode different REN isoforms.

Model organisms

Ren1 knockout mouse phenotype

Characteristic      Phenotype

Model organisms have been used in the study of REN function. A knockout mouse line, called Ren1Ren-1c Enhancer KO was generated.[15] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Homozygous mutant animals had a decreased heart rate and an increased susceptibility to bacterial infection. A more detailed analysis of this line indicated plasma creatinine was also increased and males had lower mean arterial pressure than controls.

Clinical applications

Renin inhibitor

An over-active renin-angiotension system leads to vasoconstriction and retention of sodium and water. These effects lead to hypertension. Therefore, renin inhibitors can be used for the treatment of hypertension.This is measured by the plasma renin activity (PRA).

In current medical practice, the renin-angiotensin-aldosterone-System’s overactivity (and resultant hypertension) is more commonly reduced using either ACE inhibitors (such as ramipril and perindopril) or angiotensin II receptor blockers (ARBs, such as losartan, irbesartan or candesartan) rather than a direct oral renin inhibitor. ACE inhibitors or ARBs are also part of the standard treatment after a heart attack.

The differential diagnosis of kidney cancer in a young patient with hypertension includes juxtaglomerular cell tumor (reninoma), Wilms’ tumor, and renal cell carcinoma, all of which may produce renin.

Measurement

Further information: Plasma renin activity

Renin is usually measured as the plasma renin activity (PRA). PRA is measured specially in case of certain diseases that present with hypertension or hypotension. PRA is also raised in certain tumors. A PRA measurement may be compared to a plasma aldosterone concentration (PAC) as a PAC/PRA ratio.

Calcitriol increases blood calcium levels ( [Ca2+] ) by promoting absorption of dietary calcium from the gastrointestinal tract and increasing renal tubular reabsorption of calcium thus reducing the loss of calcium in the urine. Calcitriol also stimulates release of calcium from bone by its action on the specific type of bone cells referred to as osteoblasts, causing them to release RANKL, which in turn activates osteoclasts.

Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. For instance, PTH also indirectly stimulates osteoclasts. However, the main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate (Pi), the counterion of Ca2+. The resulting decrease in serum phosphate causes Ca5(PO4)3OH to dissolve out of bone thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).

Many of the effects of calcitriol are mediated by its interaction with the calcitriol receptor, also called the vitamin D receptor or VDR. For instance, the unbound inactive form of the calcitriol receptor in intestinal epithelial cells resides in the cytoplasm. When calcitriol binds to the receptor, the ligand-receptor complex translocates to the cell nucleus, where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein. The levels of the calcium binding protein increase enabling the cells to actively transport more calcium (Ca2+) from the intestine across the intestinal mucosa into the blood.

The maintenance of electroneutrality requires that the transport of Ca2+ ions catalyzed by the intestinal epithelial cells be accompanied by counterions, primarily inorganic phosphate. Thus calcitriol also stimulates the intestinal absorption of phosphate.The observation that calcitriol stimulates the release of calcium from bone seems contradictory, given that sufficient levels of serum calcitriol generally prevent overall loss of calcium from bone. It is believed that the increased levels of serum calcium resulting from calcitriol-stimulated intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts. Only when there are conditions, such as dietary calcium deficiency or defects in intestinal transport, which result in a reduction of serum calcium does an overall loss of calcium from bone occur.

Calcitriol also inhibits the release of calcitonin,[citatioeeded] a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.(The effect of calcitonin on renal excretion is disputed.)

he prostaglandins are a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.

They are mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue. Prostaglandins are not endocrine hormones, but autocrine or paracrine, which are locally acting messenger molecules. They differ from hormones in that they are not produced at a discrete site but in many places throughout the human body. Also, their target cells are present in the immediate vicinity of the site of their secretion (of which there are many).

The prostaglandins, together with the thromboxanes and prostacyclins, form the prostanoid class of fatty acid derivatives, a subclass of eicosanoids.

The abbreviation for “prostaglandin” is PG; specific prostaglandins are named with a letter (which indicates the type of ring structure) followed by a number (which indicates the number of double bonds in the hydrocarbon structure). For example, prostaglandin E1 is abbreviated PGE1 or PGE1, and prostaglandin I2 is abbreviated PGI2 or PGI2. The number is traditionally subscripted when the context allows, but as with many similar subscript-containing nomenclatures, the subscript is simply forgone in many database fields that can store only plain text (such as PubMed bibliographic fields), and readers are used to seeing and writing it without subscript.

Function

There are currently ten known prostaglandin receptors on various cell types. Prostaglandins ligate a sub-family of cell surface seven-transmembrane receptors, G-protein-coupled receptors. These receptors are termed DP1-2, EP1-4, FP, IP1-2, and TP, corresponding to the receptor that ligates the corresponding prostaglandin (e.g., DP1-2 receptors bind to PGD2).

The diversity of receptors means that prostaglandins act on an array of cells and have a wide variety of effects such as:

cause constriction or dilation in vascular smooth muscle cells

cause aggregation or disaggregation of platelets

sensitize spinal neurons to pain

induce labor

decrease intraocular pressure

regulate inflammatory mediation

regulate calcium movement

control hormone regulation

control cell growth

acts on thermoregulatory center of hypothalamus to produce fever

acts on mesangial cells in the glomerulus of the kidney to increase glomerular filtration rate

acts on parietal cells in the stomach wall to inhibit acid secretion

brain masculinization (in rats at least) (ref : http://www.jneurosci.org/content/33/7/2761.full.pdf+html)

Prostaglandins are potent but have a short half-life before being inactivated and excreted. Therefore, they send only paracrine (locally active) or autocrine (acting on the same cell from which it is synthesized) signals.

 Pronephros

During approximately day 22 of human gestation, the paired pronephroi appear towards the cranial end of the intermediate mesoderm. In this region, epithelial cells arrange themselves in a series of tubules called nephrotomes and join laterally with the pronephric duct, which does not reach the outside of the embryo. Thus the pronephros is considered nonfunctional in mammals because it cannot excrete waste from the embryo.

Mesonephros

Each pronephric duct grows towards the tail of the embryo, and in doing so induces intermediate mesoderm in the thoracolumbar area to become epithelial tubules called mesonephric tubules. Each mesonephric tubule receives a blood supply from a branch of the aorta, ending in a capillary tuft analogous to the glomerulus of the definitive nephron. The mesonephric tubule forms a capsule around the capillary tuft, allowing for filtration of blood. This filtrate flows through the mesonephric tubule and is drained into the continuation of the pronephric duct, now called the mesonephric duct or Wolffian duct. The nephrotomes of the pronephros degenerate while the mesonephric duct extends towards the most caudal end of the embryo, ultimately attaching to the cloaca. The mammalian mesonephros is similar to the kidneys of aquatic amphibians and fishes.

Metanephros

During the fifth week of gestation, the mesonephric duct develops an outpouching, the ureteric bud, near its attachment to the cloaca. This bud, also called the metanephrogenic diverticulum, grows posteriorly and towards the head of the embryo. The elongated stalk of the ureteric bud, the metanephric duct, later forms the ureter. As the cranial end of the bud extends into the intermediate mesoderm, it undergoes a series of branchings to form the collecting duct system of the kidney. It also forms the major and minor calyces and the renal pelvis.

The portion of undifferentiated intermediate mesoderm in contact with the tips of the branching ureteric bud is known as the metanephrogenic blastema. Signals released from the ureteric bud induce the differentiation of the metanephrogenic blastema into the renal tubules. As the renal tubules grow, they come into contact and join with connecting tubules of the collecting duct system, forming a continuous passage for flow from the renal tubule to the collecting duct. Simultaneously, precursors of vascular endothelial cells begin to take their position at the tips of the renal tubules. These cells differentiate into the cells of the definitive glomerulus.

 Terms

Microscopic shot of the renal cortex.

Microscopic shot of the renal medulla.

• renal capsule: The membranous covering of the kidney.

• cortex: The outer layer over the internal medulla. It contains blood vessels, glomeruli (which are the kidneys’ “filters”) and urine tubes and is supported by a fibrous matrix.

• hilus: The opening in the middle of the concave medial border for nerves and blood vessels to pass into the renal sinus.

• renal column: The structures which support the cortex. They consist of lines of blood vessels and urinary tubes and a fibrous material.

• renal sinus: The cavity which houses the renal pyramids.

• calyces: The recesses in the internal medulla which hold the pyramids. They are used to subdivide the sections of the kidney. (singular – calyx)

• papillae: The small conical projections along the wall of the renal sinus. They have openings through which urine passes into the calyces. (singular – papilla)

• renal pyramids: The conical segments within the internal medulla. They contain the secreting apparatus and tubules and are also called malpighian pyramids.

• renal artery: Two renal arteries come from the aorta, each connecting to a kidney. The artery divides into five branches, each of which leads to a ball of capillaries. The arteries supply (unfiltered) blood to the kidneys. The left kidney receives about 60% of the renal bloodflow.

• renal vein: The filtered blood returns to circulation through the renal veins which join into the inferior vena cava.

• renal pelvis: Basically just a funnel, the renal pelvis accepts the urine and channels it out of the hilus into the ureter.

• ureter: A narrow tube 40 cm long and 4 mm in diameter. Passing from the renal pelvis out of the hilus and down to the bladder. The ureter carries urine from the kidneys to the bladder by means of peristalsis.

• renal lobe: Each pyramid together with the associated overlying cortex forms a renal lobe

Diseases and disorders

Congenital

• Congenital hydronephrosis

• Congenital obstruction of urinary tract

• Duplicated ureter

• Horseshoe kidney

• Polycystic kidney disease

• Renal dysplasia

• Unilateral small kidney

Acquired

• Diabetic nephropathy

• Glomerulonephritis

• Hydronephrosis is the enlargement of one or both of the kidneys caused by obstruction of the flow of urine.

• Interstitial nephritis

• Kidney stones are a relatively common and particularly painful disorder.

• Kidney tumors

• Wilms tumor

• Renal cell carcinoma

• Lupus nephritis

• Minimal change disease

• In nephrotic syndrome, the glomerulus has been damaged so that a large amount of protein in the blood enters the urine. Other frequent features of the nephrotic syndrome include swelling, low serum albumin, and high cholesterol.

• Pyelonephritis is infection of the kidneys and is frequently caused by complication of a urinary tract infection.

• Renal failure

• Acute renal failure

• Chronic renal failure

THE FORMATION OF URINE

FIGURATION, REABSORPTION, AND SECRETION

Every one of us depends on the process of urination for the removal of certain waste products in the body. The production of urine is vital to the health of the body. Most of us have probably never thought of urine as valuable, but we could not survive if we did not produce it and eliminate it. Urine is composed of water, certain electrolytes, and various waste products that are filtered out of the blood system. Remember, as the blood flows through the body, wastes resulting from the metabolism of foodstuffs in the body cells are deposited into the bloodstream, and this waste must be disposed of in some way. A major part of this “cleaning” of the blood takes place in the kidneys and, in particular, in the nephrons, where the blood is filtered to produce the urine. Both kidneys in the body carry out this essential blood cleansing function. Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration. This is called the filtration fraction. The rest of the blood (about 80%) does not go through the filtering portion of the kidney, but flows through the rest of the body to service the various nutritional, respiratory, and other needs that are always present.

For the production of urine, the kidneys do not simply pick waste products out of the bloodstream and send them along for final disposal. The kidneys’ 2 million or more nephrons (about a million in each kidney) form urine by three precisely regulated processes: filtration, reabsorption, and secretion.

Filtration

Urine formation begins with the process of filtration, which goes on continually in the renal corpuscles . As blood courses through the glomeruli, much of its fluid, containing both useful chemicals and dissolved waste materials, soaks out of the blood through the membranes (by osmosis and diffusion) where it is filtered and then flows into the Bowman’s capsule. This process is called glomerular filtration. The water, waste products, salt, glucose, and other chemicals that have been filtered out of the blood are known collectively as glomerular filtrate. The glomerular filtrate consists primarily of water, excess salts (primarily Na⁺ and K⁺), glucose, and a waste product of the body called urea. Urea is formed in the body to eliminate the very toxic ammonia products that are formed in the liver from amino acids. Since humans cannot excrete ammonia, it is converted to the less dangerous urea and then filtered out of the blood. Urea is the most abundant of the waste products that must be excreted by the kidneys. The total rate of glomerular filtration (glomerular filtration rate or GFR) for the whole body (i.e., for all of the nephrons in both kidneys) is normally about 125 ml per minute. That is, about 125 ml of water and dissolved substances are filtered out of the blood per minute. The following calculations may help you visualize how enormous this volume is. The GFR per hour is:

125 ml/min X 60min/hr= 7500 ml/hr.

The GFR per day is: 7500 ml/hr X 24 hr/day = 180,000 ml/day or 180 liters/day.

Now, see if you can calculate how many gallons of water we are talking about. Here are some conversion factors for you to consider: 1 quart = 960 ml, 1 liter = 1000 ml,

4 quarts. = 1 gallon. Remember to cancel units and you will have no problem.

Now, what we have just calculated is the amount of water that is removed from the blood each day – about 180 liters per day. (Actually it also includes other chemicals, but the vast majority of this glomerular filtrate is water.) Imagine the size of a 2-liter bottle of soda pop. About 90 of those bottles equals 180 liters! Obviously no one ever excretes anywhere near 180 liters of urine per day! Why? Because almost all of the estimated 43 gallons of water (which is about the same as 180 liters – did you get the right answer?) that leaves the blood by glomerular filtration, the first process in urine formation, returns to the blood by the second process – reabsorption.

Blood is a bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells.

In vertebrates, it is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is mostly water (92% by volume), and contains dissipated proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and blood cells themselves. Albumin is the main protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. The blood cells are mainly red blood cells (also called RBCs or erythrocytes) and white blood cells, including leukocytes and platelets. The most abundant cells in vertebrate blood are red blood cells. These contain hemoglobin, an iron-containing protein, which facilitates transportation of oxygen by reversibly binding to this respiratory gas and greatly increasing its solubility in blood. In contrast, carbon dioxide is almost entirely transported extracellularly dissolved in plasma as bicarbonate ion.

Vertebrate blood is bright red when its hemoglobin is oxygenated. Some animals, such as crustaceans and mollusks, use hemocyanin to carry oxygen, instead of hemoglobin. Insects and some mollusks use a fluid called hemolymph instead of blood, the difference being that hemolymph is not contained in a closed circulatory system. In most insects, this “blood” does not contain oxygen-carrying molecules such as hemoglobin because their bodies are small enough for their tracheal system to suffice for supplying oxygen.

Jawed vertebrates have an adaptive immune system, based largely on white blood cells. White blood cells help to resist infections and parasites. Platelets are important in the clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune system.

Blood is circulated around the body through blood vessels by the pumping action of the heart. In animals with lungs, arterial blood carries oxygen from inhaled air to the tissues of the body, and venous blood carries carbon dioxide, a waste product of metabolism produced by cells, from the tissues to the lungs to be exhaled.

Medical terms related to blood often begin with hemo- or hemato- (also spelled haemo- and haemato-) from the Greek word αἷμα (haima) for “blood”. In terms of anatomy and histology, blood is considered a specialized form of connective tissue, given its origin in the bones and the presence of potential molecular fibers in the form of fibrinogen.

Functions

Blood performs many important functions within the body including:

Supply of oxygen to tissues (bound to hemoglobin, which is carried in red cells)

Supply of nutrients such as glucose, amino acids, and fatty acids (dissolved in the blood or bound to plasma proteins (e.g., blood lipids))

Removal of waste such as carbon dioxide, urea, and lactic acid

Immunological functions, including circulation of white blood cells, and detection of foreign material by antibodies

Coagulation, which is one part of the body’s self-repair mechanism (blood clotting after an open wound in order to stop bleeding)

Messenger functions, including the transport of hormones and the signaling of tissue damage

Regulation of body pH

Regulation of core body temperature

Hydraulic functions

Reabsorption

Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) because these substances have already been absorbed once (particularly in the intestines).

Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport.

Indirect reabsorption

In some cases, reabsorption is indirect. For example, bicarbonate (HCO3-) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger:

In the lumen

The H+ combines with HCO3- to form carbonic acid (H2CO3)

Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2

CO2 freely diffuses into the cell

In the epithelial cell

Cytoplasmic carbonic anhydrase converts the CO2 and H2O (which is abundant in the cell) into H2CO3

H2CO3 readily dissociates into H+ and HCO3-

HCO3- is facilitated out of the cell’s basolateral membrane

Hormones

Some key regulatory hormones for reabsorption include:

aldosterone, which stimulates active sodium reabsorption (and water as a result)

antidiuretic hormone, which stimulates passive water reabsorption

Both hormones exert their effects principally on the collecting ducts.

Reabsorption, by definition, is the movement of substances out of the renal tubules back into the blood capillaries located around the tubules (called the peritubular copillaries).

Substances reabsorbed are water, glucose and other nutrients, and sodium (Na⁺) and other ions. Reabsorption begins in the proximal convoluted tubules and continues in the loop of Henle, distal convoluted tubules, and collecting tubules (Figure 3). Let’s discuss for a moment the three main substances that are reabsorbed back into the bloodstream.

Large amounts of water – more than 178 liters per day – are reabsorbed back into the bloodstream from the proximal tubules because the physical forces acting on the water in these tubules actually push most of the water back into the blood capillaries. In other words, about 99% of the 180 liters of water that leave the blood each day by glomerular filtration returns to the blood from the proximal tubule through the process of passive reabsorption.

The nutrient glucose (blood sugar) is entirely reabsorbed back into the blood from the proximal tubules. In fact, it is actively transported out of the tubules and into the peritubular capillary blood. None of this valuable nutrient is wasted by being lost in the urine. However, even when the kidneys are operating at peak efficiency, the nephrons can reabsorb only so much sugar and water. Their limitations are dramatically illustrated in cases of diabetes mellitus, a disease which causes the amount of sugar in the blood to rise far above normal. As already mentioned, in ordinary cases all the glucose that seeps out through the glomeruli into the tubules is reabsorbed into the blood. But if too much is present, the tubules reach the limit of their ability to pass the sugar back into the bloodstream, and the tubules retain some of it. It is then carried along in the urine, often providing a doctor with her first clue that a patient has diabetes mellitus. The value of urine as a diagnostic aid has been known to the world of medicine since as far back as the time of Hippocrates. Since then, examination of the urine has become a regular procedure for physicians as well as scientists.

Sodium ions (Na⁺) and other ions are only partially reabsorbed from the renal tubules back into the blood. For the most part, however, sodium ions are actively transported back into blood from the tubular fluid. The amount of sodium reabsorbed varies from time to time; it depends largely on how much salt we take in from the foods that we eat. (As stated earlier, sodium is a major component of table salt, known chemically as sodium chloride.) As a person increases the amount of salt taken into the body, that person’s kidneys decrease the amount of sodium reabsorption back into the blood. That is, more sodium is retained in the tubules. Therefore, the amount of salt excreted in the urine increases. The process works the other way as well. The less the salt intake, the greater the amount of sodium reabsorbed back into the blood, and the amount of salt excreted in the urine decreases.

Renal glucose reabsorption is the part of renal physiology that deals with the retrieval of filtered glucose, preventing it from disappearing from the body through the urine.

If glucose is not reabsorbed by the kidney, it appears in the urine, in a condition known as glucosuria. This is associated with diabetes mellitus.

Selective Reabsorption of glucose is achieved by a combination of processes.

Firstly, the glucose in the proximal tubule is co-transported with sodium ions into the proximal convoluted tubule walls. Some (typically smaller) amino acids are also transported in this way. Once in the tubule wall, the glucose and amino acids diffuse directly into the blood capillaries along a concentration gradient. This blood is flowing, so the gradient is maintained. Lastly, sodium/potassium ion active transport pumps remove sodium from the tubule wall and the sodium is put back into the blood. This maintains a sodium concentration gradient in the proximal tubule lining, so the first step continues to happen.

Renal protein reabsorption is the part of renal physiology that deals with the retrieval of filtered proteins, preventing them from disappearing from the body through the urine.

Almost all reabsorption takes place in the proximal tubule. Only ~1% is left in the final urine.

The proteins cross the apical membrane by endocytosis. They are subsequently degraded in lysosomes. The remaining free amino acids are transported across the basolateral membrane by amino acid transporters.

Renal oligopeptide reabsorption is the part of renal physiology that deals with the retrieval of filtered oligopeptides, preventing them from disappearing from the body through the urine.

Almost all reabsorption takes place in the proximal tubule. Practically nothing is left in the final urine. Longer oligopeptides, such as angiotensi nand glutathioneare degraded by enzymes on the brush border, while shorter ones, such as carnosine, are transported across the apical membrane as a whole by the PepT 1 transporter, and degraded inside the proximal tubule cell.

Amino acids  are biologically important organic compounds made from amine (-NH2) and carboxylic acid (-COOH) functional groups, along with a side-chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen, though other elements are found in the side-chains of certain amino acids. About 500 amino acids are known and can be classified in many ways. Structurally they can be classified according to the functional groups’ locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.) In the form of proteins, amino acids comprise the second largest component (after water) of human muscles, cells and other tissues.Outside proteins, amino acids perform critical roles in processes such as neurotransmitter transport and biosynthesis.

Amino acids having both the amine and carboxylic acid groups attached to the first (alpha-) carbon atom have particular importance in biochemistry. They are known as 2-, alpha-, or α-amino acids (generic formula H2NCHRCOOH in most cases where R is an organic substituent known as a “side-chain”); often the term “amino acid” is used to refer specifically to these. They include the 22 proteinogenic (“protein-building”) amino acids which combine into peptide chains (“polypeptides”) to form the building blocks of a vast array of proteins. These are all L-stereoisomers (“left-handed” isomers) although a few D-amino acids (“right-handed”) occur in bacterial envelopes and some antibiotics.Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as “standard” amino acids. The other two (“non-standard” or “non-canonical”) are pyrrolysine (found in methanogenic organisms and other eukaryotes) and selenocysteine (present in many noneukaryotes as well as most eukaryotes). For example, 25 human proteins include selenocysteine (Sec) in their primary structure,[10] and the structurally characterized enzymes (selenoenzymes) employ Sec as the catalytic moiety in their active sites. Pyrrolysine and selenocysteine are encoded via variant codons; for example, selenocysteine is encoded by stop codon and SECIS element.Codon–tRNA combinations not found iature can also be used to “expand” the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids.

Many important proteinogenic and non-proteinogenic amino acids also play critical non-protein roles within the body. For example: in the human brain, glutamate (standard glutamic acid) and gamma-amino-butyric acid (“GABA”, non-standard gamma-amino acid) are respectively the main excitatory and inhibitory neurotransmitters;hydroxyproline (a major component of the connective tissue collagen) is synthesised from proline; the standard amino acid glycine is used to synthesise porphyrins used in red blood cells; and the non-standard carnitine is used in lipid transport.

9 of the 20 standard amino acids are called “essential” for humans because they cannot be created from other compounds by the human body, and so must be taken in as food. Others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species.

Because of their biological significance, amino acids are important iutrition and are commonly used iutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics and chiral catalysts.

Renal urea handling is the part of renal physiology that deals with the reabsorption and secretion of urea. Movement of large amounts of urea across cell membranes is made possible by urea transporter proteins.

Urea allows the kidneys to create hyperosmotic urine (urine that has more ions in it – is “more concentrated” – than that same person’s blood plasma). Preventing the loss of water in this manner is important if the person’s body must save water in order to maintain a suitable blood pressure or (more likely) in order to maintain a suitable concentration of sodium ions in the blood plasma.

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

It is regulated by antidiuretic hormone, which controls the amount reabsorbed in the collecting duct system and secreted into the loop of Henle

Renal reabsorption of sodium (Na+) is a part of renal physiology. It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide.

It is very efficient, since more than 25,000 mmoles/day of sodium is filtered into the nephron, but only ~100 mmoles/day, or less than 0.4% remains in the final urine.

Water is a chemical compound with the chemical formula H

 2O. A water molecule contains one oxygen and two hydrogen atoms

connected by covalent bonds. Water is a liquid at standard ambient temperature and pressure, but it often co-exists on Earth with its solid state, ice, and gaseous state (water vapor or steam). Water also exists in a liquid crystal state near hydrophilic surfaces.

Water covers 71% of the Earth’s surface, and is vital for all known forms of life.On Earth, 96.5% of the planet’s water is found in seas and oceans, 1.7% in groundwater, 1.7% in glaciers and the ice caps of Antarctica and Greenland, a small fraction in other large water bodies, and 0.001% in the air as vapor, clouds (formed of solid and liquid water particles suspended in air), and precipitation. Only 2.5% of the Earth’s water is freshwater, and 98.8% of that water is in ice and groundwater. Less than 0.3% of all freshwater is in rivers, lakes, and the atmosphere, and an even smaller amount of the Earth’s freshwater (0.003%) is contained within biological bodies and manufactured products.

Water on Earth moves continually through the water cycle of evaporation and transpiration (evapotranspiration), condensation, precipitation, and runoff, usually reaching the sea. Evaporation and transpiration contribute to the precipitation over land.

Safe drinking water is essential to humans and other lifeforms even though it provides no calories or organic nutrients. Access to safe drinking water has improved over the last decades in almost every part of the world, but approximately one billion people still lack access to safe water and over 2.5 billion lack access to adequate sanitation.There is a clear correlation between access to safe water and GDP per capita.However, some observers have estimated that by 2025 more than half of the world population will be facing water-based vulnerability. A recent report (November 2009) suggests that by 2030, in some developing regions of the world, water demand will exceed supply by 50%. Water plays an important role in the world economy, as it functions as a solvent for a wide variety of chemical substances and facilitates industrial cooling and transportation. Approximately 70% of the fresh water used by humans goes to agriculture.

Secretion

Now, let’s describe the third important process in the formation of urine. Secretion is the process by which substances move into the distal and collecting tubules from blood in the capillaries around these tubules (Figure 3). In this respect, secretion is reabsorption in reverse. Whereas reabsorption moves substances out of the tubules and into the blood, secretion moves substances out of the blood and into the tubules where they mix with the water and other wastes and are converted into urine. These substances are secreted through either an active transport mechanism or as a result of diffusion across the membrane. Substances secreted are hydrogen ions (H+), potassium ions (K+), ammonia (NH3), and certain drugs. Kidney tubule secretion plays a crucial role in maintaining the body’s acid-base balance, another example of an important body function that the kidney participates in.

The organs involved in regulation of external acid-base balance are the lungs are the kidneys.

The lungs are important for excretion of carbon dioxide (the respiratory acid) and there is a huge amount of this to be excreted: at least 12,000 to 13,000 mmols/day.

In contrast the kidneys are responsible for excretion of the fixed acids and this is also a critical role even though the amounts involved (70-100 mmols/day) are much smaller. The main reason for this renal importance is because there is no other way to excrete these acids and it should be appreciated that the amounts involved are still very large when compared to the plasma [H⁺] of only 40 nanomoles/litre.

There is a second extremely important role that the kidneys play in acid-base balance, namely the reabsorption of the filtered bicarbonate. Bicarbonate is the predominant extracellular buffer against the fixed acids and it important that its plasma concentration should be defended against renal loss.

In acid-base balance, the kidney is responsible for 2 major activities:

·                   Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol/day

·                   Excretion of the fixed acids (acid anion and associated H⁺): about 1 mmol/kg/day.

Both these processes involve secretion of H⁺ into the lumen by the renal tubule cells but only the second leads to excretion of H⁺ from the body.

The renal mechanisms involved in acid-base balance can be difficult to understand so as a simplification we will consider the processes occurring in the kidney as involving 2 aspects:

·                   Proximal tubular mechanism

·                   Distal tubular mechanism

Proximal Tubular Mechanism

The contributions of the proximal tubules to acid-base balance are:

·                   firstly, reabsorption of bicarbonate which is filtered at the glomerulus

·                   secondly, the production of ammonium

Bicarbonate Reabsorption

Daily filtered bicarbonate equals the product of the daily glomerular filtration rate (180 l/day) and the plasma bicarbonate concentration (24 mmol/l). This is 180 x 24 = 4320 mmols/day (or usually quoted as between 4000 to 5000 mmols/day).

About 85 to 90% of the filtered bicarbonate is reabsorbed in the proximal tubule and the rest is reabsorbed by the intercalated cells of the distal tubule and collecting ducts.

The reactions that occur are outlined in the diagram. Effectively, H⁺ and HCO3^– are formed from CO₂ and H₂O in a reaction catalysed by carbonic anhydrase. The actual reaction involved is probably formation of H⁺ and OH^– from water, then reaction of OH^– with CO₂ (catalysed by carbonic anhydrase) to produce HCO3^–. Either way, the end result is the same.

The H⁺ leaves the proximal tubule cell and enters the PCT lumen by 2 mechanisms:

·                   Via a Na⁺-H⁺ antiporter (major route)

·                   Via H⁺-ATPase (proton pump)

Filtered HCO3^– cannot cross the apical membrane of the PCT cell. Instead it combines with the secreted H⁺ (under the influence of brush border carbonic anhydrase) to produce CO₂ and H₂O. The CO₂ is lipid soluble and easily crosses into the cytoplasm of the PCT cell. In the cell, it combines with OH^– to produce bicarbonate. The HCO₃^– crosses the basolateral membrane via a Na⁺-HCO₃^– symporter. This symporter is electrogenic as it transfers three HCO₃– for every one Na+. In comparison, the Na⁺-H⁺ antiporter in the apical membrane is not electrogenic because an equal amount of charge is transferred in both directions.

The basolateral membrane also has an active Na⁺-K⁺ ATPase (sodium pump) which transports 3 Na⁺ out per 2 K⁺ in. This pump is electrogenic in a direction opposite to that of the Na⁺-HCO₃^– symporter. Also the sodium pump keeps intracellular Na⁺ low which sets up the Na⁺ concentration gradient required for the H⁺-Na⁺ antiport at the apical membrane. The H⁺-Na⁺ antiport is an example of secondary active transport.

The net effect is the reabsorption of one molecule of HCO₃ and one molecule of Na⁺ from the tubular lumen into the blood stream for each molecule of H⁺ secreted. This mechanism does not lead to the net excretion of any H⁺ from the body as the H⁺ is consumed in the reaction with the filtered bicarbonate in the tubular lumen.

[Note: The differences in functional properties of the apical membrane from that of the basolateral membranes should be noted. This difference is maintained by the tight junctions which link adjacent proximal tubule cells. These tight junctions have two extremely important functions:

Gate function: They limit access of luminal solutes to the intercellular space. This resistance can be altered and this paracellular pathway can be more open under some circumstances (ie the ‘gate’ can be opened a little).

Fence function: The junctions maintain different distributions of some of the integral membrane proteins. For example they act as a ‘fence’ to keep the Na⁺-H⁺ antiporter limited to the apical membrane, and keep the Na⁺-K⁺ ATPase limited to the basolateral membrane. The different distribution of such proteins is absolutely essential for cell function.

The 4 major factors which control bicarbonate reabsorption are:

·                   Luminal HCO₃^– concentration

·                   Luminal flow rate

·                   Arterial pCO₂

·                   Angiotensin II (via decrease in cyclic AMP)

An increase in any of these four factors causes an increase in bicarbonate reabsorption. Parathyroid hormone also has an effect: an increase in hormone level increases cAMP and decreases bicarbonate reabsorption.

The mechanism for H⁺ secretion in the proximal tubule is described as a high capacity, low gradient system:

The high capacity refers to the large amount (4000 to 5000 mmols) of H⁺ that is secreted per day. (The actual amount of H⁺ secretion is 85% of the filtered load of HCO₃^–).

The low gradient refers to the low pH gradient as tubular pH can be decreased from 7.4 down to 6.7-7.0 only.

Though no net excretion of H⁺ from the body occurs, this proximal mechanism is extremely important in acid-base balance. Loss of bicarbonate is equivalent to an acidifying effect and the potential amounts of bicarbonate lost if this mechanism fails are very large.

Mechanism of urination

The action potentials are carried by sensory neurons to the sacral segments of the spinal cord through the pelvic nerves and the parasympathetic fibers carry the action potentials to the urinary bladder in the pelvic nerves. This causes the wall of the bladder to contract. In addition, decreased somatic motor action potentials cause the external urinary sphincter, which consists of skeletal muscle, to relax. When the external urinary sphincter is relaxed urine will flow from the urinary bladder when the pressure there is great enough to force urine to flow through the urethra. The micturition reflex normally produces a series of contractions of the urinary bladder.

Action potentials carried by sensory neurons from stretch receptors in the urinary bladder wall also ascend the spinal cord to a micturition center in the pons and to the cerebrum. Descending potentials are sent from these areas of the brain to the sacral region of the spinal cord, where they modify the activity of the micturition reflex in the spinal cord. The micturition reflex, integrated in the spinal cord, predominates in infants. The ability to voluntarily inhibit micturition develops at the age of 2-3 years, and subsequently, the influence of the pons and cerebrum on the spinal micturition reflex predominates. The micturition reflex integrated in the spinal cord is automatic, but it is either stimulated or inhibited by descending action potentials. Higher brain centers prevent micturition by sending action potentials from the cerebrum and pons through spinal pathways to inhibit the spinal micturition reflex. Consequently, parasympathetic stimulation of the urinary bladder is inhibited and somatic motor neurons that keep the external urinary sphincter contracted are stimulated.

The pressure in the urinary bladder increases rapidly once its volume exceeds approximately 400-500 ml, and there is an increase in the frequency of action potentials carried by sensory neurons. The increased frequency of action potentials conducted by the ascending spinal pathways to the pons and cerebrum results in an increased desire to urinate.

Voluntary initiation of micturition involves an increase in action potentials sent from the cerebrum to facilitate the micturition reflex and to voluntarily relax the external urinary sphincter. In addition to facilitating the micturition reflex, there is an increased voluntary contraction of abdominal muscles, which causes an increase in abdominal pressure. This enhances the micturition reflex by increasing the pressure applied to the urinary bladder wall.

 

References:

1. Review of Medical Physiology // W.F.Ganong. – 24th edition, 2012.

2. Textbook of Medical Physiology // A.C.Guyton, J.E.Hall. – Eleventh edition, 2005.

3. Physiology // V.M.Moroz, O.A. Shandra. – Vinnytsia. – Nova khyha Publishers, 2011