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LFT

LFT

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patient's liver. Most liver diseases cause only mild symptoms initially, while it is vital that these diseases are detected early. Hepatic involvement in some diseases can be of crucial importance.

Regular liver panel

Total Protein (TP)

The liver produces most of the plasma proteins in the body. So it makes sense to measure the amount of protein in the blood. Reference range (60-80 g/L).

Albumin (Alb)

Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein; the remaining fraction is called globulin (including e.g. the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to hypoalbuminaemia. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function, coagulation factors (see below) are much more sensitive. The reference range is 30-50 g/L.

Alanine transaminase (ALT)

Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L in most laboratories.

Alkaline phosphatase (ALP)

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. If there is an obstruction in the bile duct, e.g. gallstones, ALP levels in plasma will rise. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled). The reference range is usually 30-120 U/L.

Total bilirubin (TBIL)

Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing this, excreting it out through bile into the instestine. Problems with the liver or blockage of the drainage of bile will cause increased levels of bilirubin, as will increased haemolysis of red cells. Direct bilirubin, or unconjugated bilirubin is often measured in tandem, especially if the total bilirubin level is elevated. Bilirubin is unconjugated before the liver modifies it for excretion. It is dangerous in babies, as it can pass the blood-brain barrier causing kernicterus.

Other tests commonly requested alongside LFTs:

Aspartate transaminase (AST)

Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage. It is also present in red cells and cardiac muscle.

Gamma glutamyl transpeptidase (GGT)

Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic).

Coagulation tests (e.g. INR)

The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function. It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively. Category:Chemical pathology

Clinical biochemistry

Chemical pathology (also known as clinical biochemistry or clinical chemistry) is the area of pathology that is generally concerned with analysis of bodily fluids. The discipline originated in the late 19th century with the use of simple chemical tests for various components of blood and urine. Subsequently other techniques were applied including the use and measurement of enzyme activities, spectrophotometry, electrophoresis and immunoassay. Most current laboratories are now highly automated and use assays that are closely monitored and quality controlled. Tests that require examination and measurement of the cells of blood, as well as blood clotting studies, are not included as these are usually grouped under haematology. All biochemical tests come under chemical pathology. These are usually performed on serum, (the yellow watery part of blood that is left after the blood has been allowed to clot and all blood cells have been removed. This is most easily done by centrifugation which packs the more dense blood cells and platelets to the bottom of the centrifuge tube, leaving the liquid serum fraction resting above the packed cells). A large laboratory will accept up to about 700 tests. Even the largest of laboratories rarely does all these tests themselves and some need to be referred to other labs. This large array of tests can be further sub-categorised into sub- specialities of:
- General or routine chemistry
- Endocrinology to do with hormones
- Immunology to do with the study of the immune system and antibodies
- Pharmacology or Toxicology to do with the study of drugs Common Chemical Pathology tests are listed in the following table.

Sodium	Potassium	Chloride
Bicarbonate	Urea	Creatinine
Calcium	Phosphate	Albumin
Bilirubin	AST	ALT
GGT	Alkaline phosphatase	Magnesium
Osmolality	Urate	Iron
Transferrin	Total protein	Globulins
Glucose	C-reactive protein	HbA1c

Health professional

A health profession is a profession in which a person exercises skill or judgment or provides a service related to:
(a) the preservation or improvement of the health of individuals, or
(b) the treatment or care of individuals who are injured, sick, disabled, or infirm. The delivery of modern health care depends on an expanding group of highly trained professionals coming together as an interdisciplinary team. Individuals are called health professionals if they participate in delivery of health care in some way. Thus, it is a rather broad term.

Examples of members of the health professions

Medical doctors have specializations on the medicine page. Often included as adjunct to allopathic medicine are osteopaths who are licensed with the same limitations and privileges as medical doctors. Dentistry, optometry, podiatry, and psychology, while separate disciplines from medicine, are often considered medical fields in the wider definition of the term. These practitioners are granted independent license to practice medicine and surgery and provide or prescribe medications within their fields. Practitioners such as physician assistants, nurse practitioners and midwives also treat patients and prescribe medication in many legal jurisdictions; however, they do so under the direction and supervision of an independently licensed practitioner. Medical professional in its broadest sense denotes a person involved in a skilled medicine or health related occupation, such as:
- physician assistants and dental hygienists
- nurses of various qualifications, and nursing assistants
- pharmacists
- Medical technologists
- hospital corpspeople in a military organisation
- paramedics and emergency medical technicians
- technicians specialising in respiratory care and x-ray photography
- trained first responders such as most lifeguards and many firefighters and police officers
- medical assistants working side by side with physicians and other members of the health care team mostly in private or group medical practices and clinics
- biomedical equipment technicians or bmets responsible for maintaining and repairing medical and patient care equipment in hospitals
- medical librarians acquire, organize and disseminate health information to health care professionals and health care consumers The foundation sciences underpinning human medicine overlap veterinary medicine, which includes both veterinarians and veterinary technicians (also veterinary technologist). See also : allied health professions alternative medicine, bioengineers, Chinese medicine, dentists, laboratory scientists, medical assistants, medicine, medical technologist, nurse, nutritionists, occupational therapists, optometry, paramedic, pharmacists, physician, physiotherapists, podiatrists, radiologists, sanitary professions, speech therapists, veterinarian Category:Healthcare

Liver

The liver is an organ in vertebrates, including humans. It plays a major role in metabolism and has a number of functions in the body including drug detoxification, glycogen storage, and plasma protein synthesis. It also produces bile, which is important for digestion. Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hepar.

Anatomy

Greek Greek The adult human liver normally weighs between 1.0 - 2.5 kilograms, and is a soft, pinkish-brown "boomerang shaped" organ. It is the largest internal organ (the largest organ being the skin) and sits immediately under the diaphragm on the right side of the upper abdomen. The liver lies on the right of the stomach and makes a kind of bed for the gallbladder (which stores bile). The liver is supplied by two major blood vessels: the hepatic artery and the portal vein. The hepatic artery normally comes off the celiac trunk. The portal vein brings venous blood from the spleen, pancreas, and small intestines, so that the liver can process the nutrients and byproducts of food digestion. The hepatic veins drain directly into the inferior vena cava. The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. These eventually drain into the right and left hepatic ducts, which in turn merge to form the common hepatic duct. The cystic duct (from the gallbladder) joins with the common hepatic duct to form the common bile duct. Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the duodenum together at the ampulla of Vater. The branchings of the bile ducts resemble those of a tree, and indeed the term "biliary tree" is commonly used in this setting. The liver is one of the only internal human organs capable of natural regeneration of lost tissue; as little as 25% of remaining liver can regenerate into a whole liver again. This is predominantly due to the hepatocytes acting as unipotential stem cells. There is also some evidence of bipotential stem cells, called oval cells, which can differentiate into either hepatocytes or cholangiocytes (cells that line the bile ducts).

Surface anatomy

Apart from a patch where it connects to the diaphragm, the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments. These "ligaments" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks. Traditional gross anatomy divided the liver into four lobes based on surface features. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe. If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe. From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Functional anatomy

For purposes such as advanced liver surgery, it is crucial to understand the organization of liver based on blood supply and biliary drainage. The central area where the common bile duct, portal vein, and hepatic artery enter the liver is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by a plane joining the gallbladder fossa to the inferior vena cava. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight segments based on secondary and tertiary branching of the blood supply. The segments corresponding to the surface anatomical lobes are as follows:

Physiology

The various functions of the liver are carried out by the liver cells or hepatocytes.
- The liver produces and excretes bile required for food digestion. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
- The liver performs several roles in carbohydrate metabolism:
- Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
- Glycogenolysis (the formation of glucose from glycogen)
- Glycogenesis (the formation of glycogen from glucose)
- The breakdown of insulin and other hormones
- The liver also performs several roles in lipid metabolism:
- Cholesterol synthesis
- The production of triglycerides (fats).
- The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, and XI, as well as protein C, protein S and antithrombin.
- The liver breaks down hemoglobin (bile pigments are its metabolites), toxic substances and most medicinal products. This sometimes results in toxication, when the metabolite is more toxic than its precursor.
- The liver converts ammonia to urea.
- The liver stores a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
- In the first trimester fetus, the liver is the main site of red blood cell production. By the 42nd week of gestation, the bone marrow has almost completely taken over that task. Producing an artificial organ or device capable of emulating all functions of the liver is outside the reach of science in the foreseeable future. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

Diseases of the liver

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
- Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
- Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals
- Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage
- Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract)
- Wilson's disease, a hereditary disease which causes the body to retain copper
- Primary sclerosing cholangitis, an inflammatory disease of the bile duct, autoimmune in nature.
- Primary biliary cirrhosis, autoimmune disease of small bile ducts
- Budd-Chiari syndrome, obstruction of the hepatic vein. A number of liver function tests are available to test the proper function of the liver. These are enzymes that are most abundant in liver tissue, metabolites or products.

Liver transplantation

Liver transplantation is an option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks. Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child. More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial as it entails performing a much larger operation on the donor, and indeed there have been at least two donor deaths out of the first several hundred cases.

Development

The liver develops as an endodermal outpocketing of the foregut called the hepatic diverticulum. Its initial blood supply is primarily from the vitelline veins that drain blood from the yolk sac. The superior part of the hepatic diverticulum gives rise to the hepatocytes and bile ducts, while the inferior part becomes the gallbladder and its associated cystic duct.

Fetal blood supply

In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and thence to the inferior vena cava, allowing placental blood to bypass the liver. After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

Analogous organs

Arthropods have a digestive gland that functions like a combination of the liver and the pancreas. In insects this organ is known as the fat body.

Liver as food

Mammal and bird livers are commonly eaten as food: products include liver paté, Leberwurst, Braunschweiger, foie gras, chopped liver and liver sashimi. Both animal and fish livers are rich in Vitamin A, cod liver oil being commonly used as a supplement. Vitamin A levels can be toxic, particularly in polar animals; the Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned, the latter fatally, from eating husky liver.

Cultural allusions

In Greek mythology, Prometheus was punished by the gods for revealing fire to humans by being chained to a rock where a vulture (or an eagle, Ethon) would peck out his liver, which would grow again overnight. Curiously, the liver is the only human internal organ that actually can regenerate itself to a certain extent, a characteristic which may have already been known to the Greeks. The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.

References

The following are standard medical textbooks.
- Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams & Wilkins, 2003. ISBN 0781730074
- Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0632055820
- David Zakim, Thomas D. Boyer. eds. Hepatology : a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0721690513
- Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0743405854
- Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1583331883. [http://www.liverdisease.com her webpage].
- Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0737300906. [http://cpmcnet.columbia.edu/dept/gi/disliv.html his Columbia U web site, Diseases of the liver ]

External links

- [http://www.aasld.org American Association for the Study of Liver Diseases] AASLD
- [http://www.liversociety.org American Liver Society] ALS
- [http://mathis.heydtmann.de/WikiLiver WikiLiver: A Wiki dedicated to the liver] Category:Abdomen Category:Digestive system ko:간 ja:肝臓 simple:Liver

Blood plasma

Blood plasma is the liquid component of blood, in which the blood cells are suspended. Serum is the same as blood plasma except that clotting factors (such as fibrin) have been removed. Plasma resembles whey in appearance (transparent with a faint straw colour). It is mainly composed of water, blood proteins, and inorganic electrolytes. It serves as transport medium for glucose, lipids, hormones, metabolic end products, carbon dioxide and oxygen. (Oxygen transport capacity of plasma is much lower than that of the hemoglobin in the red blood cells; it may increase under hyperbaric conditions.) Plasma is the storage and transport medium of clotting factors and its protein content is necessary to maintain the oncotic pressure of the blood.

Laboratory use of plasma and serum

For purposes of laboratory tests, plasma is obtained from whole blood. To prevent clotting, an anticoagulant such as citrate or heparin is added to the blood specimen immediately after it is obtained. (Usually the anticoagulant is already in the evacuated blood collection tube (e.g. Vacutainer or Vacuette®) when the patient is bled.) The specimen is then centrifuged to separate plasma from blood cells. Plasma can be frozen below -80°C nearly indefinitely for subsequent analysis or use. This blood product derivative is known as fresh frozen plasma (FFP). For many biochemical laboratory tests, plasma and blood serum can be used interchangeably. Serum resembles plasma in composition but lacks the coagulation factors. It is obtained by letting a blood specimen clot prior to centrifugation. For this purpose, a serum-separating tube (SST) can be used which contains an inert catalyst (such as glass beads or powder) to facilitate clotting as well as a portion of gel with a density designed to sit between the liquid and cellular layers in the tube after centrifugation, making separation more convenient. Tests of coagulation (such as the INR and aPTT) require all clotting factors to be preserved. Serum, therefore, is inappropriate for these tests. A citrated evacuated blood collection tube (e.g. Vacutainer or Vacuette) is usually used, as the anticoagulant effects of citrate is dependent upon concentration and can be reversed for testing. Serum is preferred for many tests as the anticoagulants in plasma can sometimes interfere with the results. Different anticoagulants interfere with different tests; using serum means the same sample can be used for many tests. In protein electrophoresis, using plasma causes an additional band to be seen, which might be mistaken for a paraprotein.

Fresh frozen plasma

Fresh frozen plasma (FFP) is prepared from a single unit of blood. It is frozen after collection and can be stored for one year from date of collection. FFP contains all of the coagulation factors and proteins present in the original unit of blood. It is used to treat coagulopathies from warfarin overdose, liver disease, or dilutional coagulopathy. FFP that has been stored more than a standard length of time is re-classified as simply "frozen plasma", which is identical except that the coagulation factors are no longer considered completely viable.

Dried plasma

liver disease Dried plasma was developed and first used during WWII. Prior to the United States involvement in the war, liquid plasma and whole blood were used. The "Blood for Britain" program during the early 1940s was quite successful (and popular stateside). Nontheless the decision was made to develop a dried plasma package for the armed forces because it reduced breakage and made transport, packaging, and storage much simpler. [http://history.amedd.army.mil/booksdocs/wwii/blood/chapter1.htm] The resulting Army-Navy dried plasma package came in two tin cans containing 400 cc bottles. One bottle contained enough distilled water to completely reconstitute the dried plasma contained in the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. [http://history.amedd.army.mil/booksdocs/wwii/blood/chapter7.htm] By the end of the war the American Red Cross had provided enough blood for over six million plasma packages. Most of the surplus plasma was returned stateside for civilian use. Serum albumin replaced dried plasma for combat use during the Korean War. [http://history.amedd.army.mil/booksdocs/wwii/blood/chapter11.htm] Category:Blood ko:혈장 ja:血漿

Protein

. This protein was the first to have its structure solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, which led to them receiving a Nobel Prize in Chemistry.]] A protein (in Greek πρωτεϊνη = first thread) is a complex, high-molecular-weight organic compound that consists of amino acids joined by peptide bonds. Proteins are essential to the structure and function of all living cells and viruses. Many proteins are enzymes or subunits of enzymes. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the cytoskeleton, serving as biological scaffolds for the mechanical integrity and tissue signalling functions. Still more functions filled by proteins include immune response and the storage and transport of various ligands. In nutrition, proteins serve as the source of amino acids for organisms that do not synthesize those amino acids natively. Proteins are one of the classes of bio-macromolecules, alongside polysaccharides, lipids, and nucleic acids, that make up the primary constituents of living things. They are among the most actively-studied molecules in biochemistry, and were discovered by Jöns Jakob Berzelius in 1838. Almost all natural proteins are encoded by DNA. DNA is transcribed to yield RNA, which serves as a template for translation by ribosomes.

Properties of Protein

Structure

ribosome Main article: Protein structure Proteins are amino acid chains that fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state, which is determined by its sequence of amino acids. Thus, proteins are their own polymers, with amino acids being the monomers. Biochemists refer to four distinct aspects of a protein's structure:
- Primary structure: the amino acid sequence
- Secondary structure: highly patterned sub-structures—alpha helix and beta sheet—or segments of chain that assume no stable shape. Secondary structures are locally defined, meaning that there can be many different secondary motifs present in one single protein molecule.
- Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structural motifs to one another
- Quaternary structure: the shape or structure that results from the union of more than one protein molecule, usually called subunit proteins subunits in this context, which function as part of the larger assembly or protein complex. In addition to these levels of structure, proteins may shift between several similar structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations," and transitions between them are called conformational changes. Proteins are separated into two groups: Complete and Incomplete. Incomplete proteins are from plants and do not include all 20 amino acids. Complete proteins come from an animal and include all 20 amino acids. You get protein from mostly everything you eat, but whether all the amino acids are in them depends on what the substance is. The primary structure is held together by covalent peptide bonds, which are made during the process of translation. The secondary structures are held together by hydrogen bonds. The tertiary structure is held together primarily by hydrophobic interactions but hydrogen bonds, ionic interactions, and disulfide bonds are usually involved too. The process by which the higher structures form is called protein folding and is a consequence of the primary structure. The mechanism of protein folding is not entirely understood. Although any unique polypeptide may have more than one stable folded conformation, each conformation has its own biological activity and only one conformation is considered to be the active, or native conformation. The two ends of the amino acid chain are referred to as the carboxy terminus (C-terminus) and the amino terminus (N-terminus) based on the nature of the free group on each extremity.

Working with proteins

Proteins are sensitive to their environment. They may only be active in their native state, over a small pH range, and under solution conditions with a minimum quantity of electrolytes. A protein in its native state is often described as folded. A protein that is not in its native state is said to be denatured. Denatured proteins generally have no well-defined secondary structure. Many proteins denature and will not remain in solution in distilled water. One of the more striking discoveries of the 20th century was that the native and denatured states in many proteins were interconvertible, that by careful control of solution conditions (by for example, dialyzing away a denaturing chemical), a denatured protein could be converted to native form. The issue of how proteins arrive at their native state is an important area of biochemical study, called the study of protein folding. Through genetic engineering, researchers can alter the sequence and hence the structure, "targeting", susceptibility to regulation and other properties of a protein. The genetic sequences of different proteins may be spliced together to create "chimeric" proteins that possess properties of both. This form of tinkering represents one of the chief tools of cell and molecular biologists to change and to probe the workings of cells. Another area of protein research attempts to engineer proteins with entirely new properties or functions, a field known as protein engineering. Protein-protein interactions can be screened for using two-hybrid screening.

Protein regulation

Various molecules and ions are able to bind to specific sites on proteins. These sites are called binding sites. They exhibit chemical specificity. The particle that binds is called a ligand. The strength of ligand-protein binding is a property of the binding site known as affinity. Since proteins are involved in practically every function performed by a cell, the mechanisms for controlling these functions therefore depend on controlling protein activity. Regulation can involve a protein's shape or concentration. Some forms of regulation include:
- Allosteric modulation: When the binding of a ligand at one site on a protein affects the binding of ligand at another site.
- Covalent modulation: When the covalent modification of a protein affects the binding of a ligand or some other aspect of the protein's function.

Diversity

Proteins are generally large molecules, having molecular masses of up to 3,000,000 (the muscle protein titin has a single amino acid chain 27,000 subunits long). Such long chains of amino acids are almost universally referred to as proteins, but shorter strings of amino acids are referred to as "polypeptides," "peptides" or rarely, "oligopeptides". The dividing line is undefined, though "polypeptide" usually refers to an amino acid chain lacking tertiary structure which may be more likely to act as a hormone (like insulin), rather than as an enzyme (which depends on its defined tertiary structure for functionality). Proteins are generally classified as soluble, filamentous or membrane-associated (see integral membrane protein). Nearly all the biological catalysts known as enzymes are soluble proteins (with a recent notable execption being the discovery of ribozymes, RNA molecules with the catalytic properties of enzymes.) Antibodies, the basis of the adaptive immune system, are another example of soluble proteins. Membrane-associated proteins include exchangers and ion channels, which move their substrates from place to place but do not change them; receptors, which do not modify their substrates but may simply shift shape upon binding them. Filamentous proteins make up the cytoskeleton of cells and much of the structure of animals: examples include tubulin, actin, collagen and keratin, all of which are important components of skin, hair, and cartilage. Another special class of proteins consists of motor proteins such as myosin, kinesin, and dynein. These proteins are "molecular motors," generating physical force which can move organelles, cells, and entire muscles. muscle

Role of Protein

Functions

Proteins are involved in practically every function performed by a cell, including regulation of cellular functions such as signal transduction and metabolism. For example, protein catabolism requires enzymes termed proteases and other enzymes such as glycosidases.

Within Nutrition

Protein is an important macronutrient to the human diet, supplying the body's needs for nitrogen and amino acids, the building blocks of proteins. The exact amount of dietary protein needed to satisfy these requirements may vary widely depending on age, sex, level of physical activity, and medical condition, as well as the RDA specified by the state. The recommended intake of protein differs from country to country, but it is marginalised between 0.8 and 1.2g / kg b.w (Per kilogram of bodyweight), however , in more serious athletes, requiring strength, the figure is somewhat between 1.0 and 2.0g per kilogram of Body weight, which is referred to as the maximum protein intake:benefits ratio. Although proteins are found in all foods, be it only in small amounts , protein is still well concentrated in foods such as legumes, nuts, and dairy products, the majority of which are protein choices for vegetarians. Protein is the major component in the regulation, growth and differentation of muscles, tendons, enzymes, skin, hair, eyes, as well as a tremendous variety of other organs and processes. The quality of protein intake is particularly important because different proteins supply essential amino acids in different proportions. Given an adequate intake of nitrogen, the human body can manufacture 10 of the 18 amino acids from glucose. The remaining 8 amino acids (threonine, valine, tryptophan, isoleucine, leucine, lysine, phenylalanine, and methionine) cannot be manufactured by the body and must be acquired through supplementation. Thus, they are termed essential amino acids. For use within the body, the majority of protein taken from food consumed is converted by protein catabolism into ammonia which, due to its toxicity, must be converted to either urea or uric acid,or in some animals is excreted in urine. Proteins possessing equal proportions of all essential amino acids in relatively abundant quantities are often termed "complete", or "High-Quality" Proteins, which are generally obtained from animal proteins, such as meat , and are rated using PDCAAS (Protein Digestibility Corrected Amino Acid Score). Despite what the name suggests, quality proteins are not essential for good supplementation or nutrition within the average person, however, the difference between amino acids in plant and animal proteins is discernable, particularly for athletes or bodybuilders as plant proteins lack two major amino acids found in animal proteins; lysine within grains, and methionine within legumes, major benefactors to a major athlete's dietary regime. Neverthelss, in terms of quality, amino acids found in plant and animal extracts are identical. Protein deficiency can lead to symptoms such as fatigue, insulin resistance, hair loss, loss of hair pigment, loss of muscle mass , low body temperature, hormonal irregularities, as well as loss of skin elsaticity . Severe protein deficiency, encountered only in times of famine, is fatal, due to the lack of material for the body to facilitate as energy. It has been known that in some "wild diets", in which people lose mass amounts of weight in a short period of time are attributed to deficiencies in protein, and thus loss in muscle mass, and not fat, which is widely known as a dangerous practice, particularly because of the benefits of muscle mass over fat. Excessive protein intake has also been linked to several problems;
- overreaction within the immune system
- liver dysfunction due to increased toxic residues
- loss of bone density, frailty of bones due to increased acidity in the blood and foundering (foot problems) in horses. It is assumed by reasearchers on the field, that excessive intake of protein forced increased calcium excretion. If there is to be excessive intake of protein, it is thought that a regular intake of calcium would be able to stablilise, or even increase the uptake of calcium by the small intestine, which would be more beneficial in older women . Proteins are often progenitors in allergies and allergic reactions to certain foods. This is because the structure of each form of protein is slightly different; some may trigger a response from the immune system while others remain perfectly safe. Many people are allergic to casein, the protein in milk; gluten, the protein in wheat and other grains; the particular proteins found in peanuts; or those in shellfish or other seafoods. It is extremely unusual for the same person to adversely react to more than two different types of proteins, due to the diversity between protein or amino acid types.

History

The first mention of the word protein, which means of first rank, were from a letter sent by Jöns Jakob "Jinglehimer Schmidt" Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where he wrote: :«Le nom protéine que je vous propose pour l’oxyde organique de la fibrine et de l’albumine, je voulais le dériver de πρωτειοξ, parce qu’il paraît être la substance primitive ou principale de la nutrition animale.» Translated as: :"The name protein that I propose for the organic oxide of fibrin and albumin, I wanted to derive from [the Greek word] πρωτειοξ, because it appears to be the primitive or principal substance of animal nutrition." Investigation of proteins and their properties had been going on since about 1800 when scientists were finding the first signs of this, at the time, unknown class of organic compounds.

References

# Kerstetter, J. E., O'Brien, K. O., Insogna, K. L. (2003) "[http://www.ajcn.org/cgi/content/full/78/3/584S Dietary protein, calcium metabolism, and skeletal homeostasis revisited]" . J Clin Endocrinol Metab Vol 78, p584S-592S. # Kerstetter, J. E., O'Brien, K. O., Caseria, D.M, Wall, D. E. & Insogna, K. L (2005) "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women" . J Clin Endocrinol Metab (2005) Vol 90, p26-31, . # Devine, A., Dick, I. M,, Islam I. M., Dhaliwal, S. S. & Prince, R. L. (2005) "Protein consumption is an important predictor of lower limb bone mass in elderly women" . Am J Clin Nutr (2005) volume 81 pages 423-428, . # Jeukendrup, A. & Gleeson, M. (2004) Sport Nutrition - An Introduction to Energy Production and Performance USA : Human Kinetics # Bean, A. (2004) Sport Nutrition for Serious Athletes London : Routledge

External links

- [http://www.expasy.uniprot.org UniProt the Universal Protein Resource]
- [http://www.proteinatlas.org Human Protein Atlas]
- [http://www.ihop-net.org/UniPub/iHOP/ iHOP - Information Hyperlinked over Proteins]
- [http://www.biochemweb.org/proteins.shtml Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology]
- [http://web.mit.edu/lms/www/ MIT's Laboratory for Protein Molecular Self-Assembly]
- [http://www.puramatrix.com/pubs Numerous publications on synthetic biomimetic protein-based biomaterials]
- [http://www.westernblotting.org Protein Research: Western Blot Protocols, Troubleshooting and Theory]
- [http://www.rcsb.org The Protein Databank: The single worldwide repository for the processing and distribution of 3-D biological macromolecular structure data.]
- [http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html Amino acid metabolism]
- [http://www.biochem.szote.u-szeged.hu/astrojan/protein2.htm Protein Images] Category:Molecular biology Category:Biochemistry Category:Nutrition zh-min-nan:Nn̄g-pe̍h-chit ko:단백질 ja:蛋白質 simple:Protein th:โปรตีน

Globulin

Globulin one of the two types of serum proteins. It is sometimes used synonymously with Globular protein; however, albumin is usually considered a globulin but not a globular protein. All other globular proteins are globulins. Protein electrophoresis is used to categorize globulins into the following four categories:
- Alpha 1 globulins
- Alpha 2 globulins
- Beta globulins
- Gamma globulins (immunoglobulins)

External links

- [http://www.drkaslow.com/html/proteins_-_albumin__globulins_.html Serum Proteins]
- [http://www.diaglab.vet.cornell.edu/clinpath/modules/chem/globulin.htm Cornell]
- [http://www.findarticles.com/p/articles/mi_m3225/is_1_71/ai_n8702975 Understanding and interpreting serum protein electrophoresis]

Cirrhosis

Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. Cirrhosis is caused by damage from toxins (including alcohol), metabolic problems, chronic viral hepatitis or other causes. Cirrhosis is sometimes referred to by its obsolete eponym Laennec's cirrhosis after René Laënnec. Cirrhosis is irreversible but treatment of the causative disease will slow or even halt the damage. Cirrhosis may refer to chronic interstitial inflammation of any tissue, but is rarely used for other diseases than cirrhosis of the liver.

Symptoms

Initial symptoms

Early symptoms include red palms, spider angioma (red spots on the upper body), hypertrophy of the parotid glands, and fibrosis of tendons in the hands. Clubbing may develop. Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:
- exhaustion
- fatigue
- loss of appetite
- nausea
- weakness
- weight loss
- abdominal pain

Complications

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.
- Bruising and bleeding due to decreased production of coagulation factors.
- Jaundice due to decreased processing of bilirubin.
- Itching due to bile products deposited in the skin.
- Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which affect cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
- Sensitivity to medication due to decreased metabolism of the active compounds.
- Hepatocellular carcinoma is primary liver cancer, commonly caused by cirrhosis. It has a high mortality rate.
- Portal hypertension - blood normally carried from the intestines and spleen through the portal vein flows more slowly and the pressure increases; this leads to the following complications:
- Ascites - fluid leaks through the vasculature into the abdominal cavity.
- Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
- Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Cirrhosis can also lead to impotence, kidney dysfunction and renal failure (hepatorenal syndrome) and osteoporosis.

Causes

Cirrhosis has many possible causes; sometimes more than one cause are present in the same patient. In the Western World, chronic alcoholism and hepatitis C are the most common causes.
- Alcoholic liver disease (ALD). Alcoholic cirrhosis develops after more than a decade of heavy drinking in 15% of all alcoholics. There is great variability in the amount of alcohol needed to cause cirrhosis (3-4 drinks a day in some men and 2-3 in some women). Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.
- Chronic hepatitis B (with or without D agent). The hepatitis B virus is probably the most common cause of cirrhosis worldwide, especially South-East Asia, but it is less common in the United States and the Western world. Hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependant on the presence of hepatitis B, but accelerates cirrhosis in co-infection.
- Chronic hepatitis C. The hepatitis C virus ranks with alcohol as a major cause of chronic liver disease and cirrhosis. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.
- Autoimmune hepatitis. This disease is caused by the immune system attacking the liver and causing inflammation, damage, and eventually scarring and cirrhosis.
- Inherited diseases. These interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.
- Alpha 1-antitrypsin deficiency
- Hemochromatosis (iron accumulation)
- Wilson's disease (copper accumulation)
- Galactosemia
- Glycogen storage diseases
- Cystic fibrosis
- Non-alcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
- Diseases that lead to chronic obstruction of the bile ducts. Accumulated bile damages liver tissue:
- In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured.
- In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred.
- Secondary biliary cirrhosis can happen after gallbladder surgery if the ducts are inadvertently tied off or injured.
- Drugs or toxins.
- Repeated bouts of heart failure with liver congestion.
- Certain parasitic infections (like schistosomiasis).
- "Cardiac cirrosis" (ICD-10 K76.1) is not a true cirrosis. It is more accurately referenced as "congestive hepatopathy", but the old name is still commonly used.

Diagnosis

The doctor may diagnose cirrhosis on the basis of symptoms, the medical history, a physical examination and laboratory tests. For example, during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present. If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, magnetic resonance imaging (MRI), or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver). A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a tiny sample of liver tissue, then examines it under the microscope for scarring or other signs of disease.

Pathology

Macroscopically, the liver is initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists in a variety of nodules with different sizes. Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Biliary tract, central vein and the radiar pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages) If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appear as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes". [http://www.pathologyatlas.ro/Cirrhosis.html 1]

Pathophysiology

The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates. Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible. The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. Iredale (2003) summarises the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile and obstructs blood flow in the circulation. In addition, it secretes TGF-β₁, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitors (TIMP 1 and 2), leading to matrix breakdown and replacement by connective tissue-secreted matrix. The fibrous tissue forms nodes, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis.

Treatment

Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Close follow-up is often necessary. Alcohol and acetaminophen, as well as other potentially damaging substances, are discouraged. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). High-protein food increases the nitrogen balance, and would theoretically increase encephalopathy; in the past, this was therefore eliminated as much as possible from the diet. Recent studies show that this assumption was incorrect, and high-protein foods are even encouraged to maintain adequate nutrition. Treatment exists of elimination of the causes and preventing complications:
- Elimination of causes: alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with chelation therapy (e.g. penicillamine) to remove the copper.
- Preventing complications. Diuretics may be necessary to suppress ascites. Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease risk of constipation; their role in preventing encephalopathy is limited. For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein. If complications cannot be controlled or when the liver ceases functioning, a liver transplant is necessary. Survival from liver transplantation has been improving over the 1990s and is now around 90%, depending largely on the severity of disease in the recipient. Transplantation necessitates the use of immune suppressants (cyclosporine or tacrolimus).

Epidemiology

In the United States, cirrhosis is the twelfth leading cause of death by disease, killing about 26,000 people each year. As it is a chronic disease with often frequent and severe complications, the cost of cirrhosis in terms of quality of life, hospital admissions, and lost productivity is high.

References

- National Digestive Diseases Information Clearinghouse (NDDIC) article Cirrhosis of the Liver [http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis NIH Publication No. 04-1134], December 2003
- Iredale JP. Cirrhosis: new research provides a basis for rational and targeted treatments. BMJ 2003;327:143-7. [http://bmj.bmjjournals.com/cgi/content/full/327/7407/143 Fulltext.]PMID 12869458
- Photos at: [http://www.pathologyatlas.ro/Cirrhosis.html Atlas of Pathology] Category:Alcohol_abuse Category:Gastroenterology ja:肝硬変

Nephrotic syndrome

Nephrotic syndrome is a disorder where the kidneys have been damaged, causing them to leak protein from the blood into the urine. It is a fairly benign disease when it occurs in childhood, but may lead on to chronic renal failure, especially in adults, or be a sign of an underlying serious disease such as systemic lupus erythematosus or a malignancy.

Signs and symptoms

The most common sign of nephrotic syndrome is excess fluid in the body. This may take the form of puffiness around the eyes, characteristically in the morning or edema over the legs which is pitting (i.e. leaves a little pit when the fluid is pressed out, which resolves over a few seconds). Fluid may also accumulated elsewhere, e.g. in the pleural cavity causing pleural effusion and the peritoneal cavity causing ascites. Occasionally, thrombosis, high levels of cholesterol , renal failure or rarely hypertension may be the first signs of nephrotic syndrome. Some patients may notice foamy urine, due to a lowering of the specific gravity by the high amount of proteinuria. Actual urinary complaints such as hematuria, or oliguria (a reduction in the amount of urine) are uncommon, and seen often in nephritic syndrome.

Diagnosis

Other causes of edema are congestive heart failure and cirrhosis. High urine levels of protein can readily be detected with a dipstick. The best way to make a diagnosis is to quantify the amount of protein in a 24-hour urine sample or a random albumin to creatinine ratio (ACR). A diagnosis of nephrotic syndrome requires more than 3.5 grams of proteinuria per 1.73 square metre surface area in adults. Additional components of the nephrotic syndrome include hypercholesterolemia and low serum albumin levels.

Pathogenesis

The glomeruli of the kidneys are the parts that normally filter the blood. They consist of capillaries that are fenestrated (leaky, due to little holes called fenestrae or windows) and that allow fluid, salts and other small solutes to flow through, but normally not proteins. In nephrotic syndrome, the glomeruli get damaged due to diabetes, glomerulonephritis or even prolonged hypertension (high blood pressure) so that that small proteins, such as albumin can pass through the kidneys into urine. Nephrotic syndrome is characterised by proteinuria (detectable protein in the urine), and low albumin levels in blood plasma. As a compensation, the liver begins to make more of all its proteins, and levels of large proteins (such as alpha 2-macroglobulin) increase. Edema usually occurs due to salt and water retention by the diseased kidneys as well as sometimes due to the reduced colloid oncotic pressure (because of reduced albumin in the plasma). Cholesterol levels are also increased, and though the mechanism isn't fully understood, it is thought to be due to the increased synthesis of lipoproteins in the liver. There is an increased tendency for thrombosis (up to 25%), perhaps due to urinary loss of inhibitors of clotting such as antithrombin III. Similar loss of immunoglobulins increases the risks of infections and relevant immunisation is recommended against pneumococcus, Haemophilus influenzae & meningococcus.

Differential diagnosis

In children, 80% of nephrotic syndrome is caused by minimal change disease, so called because on renal biopsy there is no change on light microscopy, only electron microscopy reveals fusion of foot processes. The other common causes are focal segmental glomerulosclerosis or IgA nephropathy (which typically presents as a mix of nephrotic syndrome and nephritic syndrome). In adults, the main causes are membranous nephropathy and focal segmental glomerulosclerosis (the names are descriptions of the changes in renal tissue on light microscopy), as well as diabetes, hypertension, and lupus erythematosus.

Treatment

When treating nephrotic syndrome, if the underlying problem is apparent, (e.g. hypertension, diabetes) then this should be addressed. Some types of nephrotic syndrome respond to therapy with steroids (especially minimal change disease) and/or other immunosuppressive therapy. Others are followed up in clinic with management of blood pressure, cholesterol levels, coagulation problems and renal failure. In most types of nephrotic syndrome, the protein excretion improves with the use of ACE inhibitor medication. This is generally used for the treatment of hypertension, but can also improve protein loss, even if the blood pressure is normal.

Prognosis

The prognosis depends on the cause of nephrotic syndrome. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. However other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).

Reference

External links

- [http://kidney.niddk.nih.gov/kudiseases/pubs/childhoodnephrotic/ Childhood Nephrotic Syndrome] - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
- [http://kidney.niddk.nih.gov/kudiseases/pubs/nephrotic/ Adult Nephrotic Syndrome] - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
- [http://www.nephcure.org/Info_aboutneph.html Nephcure] - a foundation that supports people coping with FSGS and nephrotic syndrome.
- [http://www.kidcomm.org KidComm] - a site devoted to kidney disorders in children. Category:Nephrology Category:Pediatrics

Nutrition

Nutrition is the study of the relationship between diet and states of health and disease. It is defined as the study of food. Absence of adequate nutrients can cause certain diseases to take hold that can potentially result in death. Between the extremes of optimal health and death from starvation or malnutrition, there is an array of disease states that can be caused or alleviated by changes in diet. Deficiencies, excesses and imbalances in the diet can produce negative impacts on health, which may result in diseases such as scurvy, obesity or osteoporosis. Also, excess ingestion of elements that have no apparent role in health (e.g. lead, mercury, PCBs, dioxins) may have toxic and potentially lethal effects depending on dose. The science of nutrition attempts to understand how and why specific aspects of diet have specific influences on health.

Overview

The human body comprises chemical compounds such as water, amino acids (proteins), fatty acids (lipids), nucleic acids (DNA/RNA), and carbohydrates (e.g. sugars). These compounds in turn consist of elements such as carbon, hydrogen, oxygen, nitrogen, and phosphorus, and may or may not contain minerals such as calcium, iron, and zinc. Minerals also ubiquitously occur in the form of salts and electrolytes. All of these chemical compounds and elements occur in various forms and combinations (e.g. hormones/vitamins, phospholipids, hydroxyapatite), both in the human body and in organisms (e.g. plants, animals) that humans eat. The human body must necessarily comprise those elements that humans eat and absorb into the bloodstream. The digestive system, except in the unborn fetus, is the first step in helping to make the different chemical compounds and elements in food available for the trillions of cells of the body. In the digestive process of an average adult, about seven (7) litres of liquid, known as digestive juices, exit the internal body and enter the lumen of the digestive tract. The digestive juices help break chemical bonds between ingested compounds as well as modulate the conformation and/or energetic state of the compounds/elements. Yet many compounds/elements are absorbed into the bloodstream unchanged, though the digestive process helps to release them from the matrix of the foods where they occur. Any unabsorbed matter is eliminated in the feces. Only a minimal amount of digestive juice is eliminated this way; the intestines reabsorb most of it otherwise the body would rapidly dehydrate (hence the devastating effects of persistent diarrhea). Study in this field must take into careful account the state of the body before ingestion and after digestion as well as the chemical content of both the food and the waste. The specific types of compounds and elements that are absorbed by the body can be determined by comparing the waste to the food. The effect that the absorbed matter has on the body can be determined by finding the difference between the pre-ingestion state and the post-digestion state. The effect may only be discernible after an extended period of time in which all food and ingestion must be exactly regulated and all waste must be analyzed. The number of variables (e.g. 'confounding factors') involved in this type of experimentation is very high. This makes scientifically valid nutritional study very time-consuming and expensive, which accounts for why a proper science of human nutrition is rather new. In general, eating a variety of fresh, whole (unprocessed) foods has proven hormonally and metabolically favourable compared to eating a monotonous diet based on processed foods. In particular, fresh, whole foods provide higher amounts and a more favourable balance of essential and vital nutrients per unit of energy, resulting in better management of cell growth, maintenance, and mitosis (cell division) as well as of appetite and energy balance. A generally more regular eating pattern (e.g. eating medium-sized meals every 3 to 4 hours) has also proven more hormonally and metabolically favourable than infrequent, haphazard food intake.

Nutrition and health

Ill health can be brought about by an imbalance of nutrients, producing either an excess or deficiency which in turn affects body functioning in a cumulative manner. Moreover, because most nutrients are, in some way or the other, involved in cell-to-cell signalling (e.g. as building block or part of a hormone or signalling 'cascades'), deficiency or excess of various nutrients affects hormonal function also indirectly. Thus, because they largely regulate the expression of genes, hormones represent a link between nutrition and how our genes are expressed, i.e. our phenotype. The strength and nature of this link are continually under investigation, but observations especially in recent years have demonstrated a pivotal role for nutrition in hormonal activity and function and therefore in health. Mineral and/or vitamin (tocotrienol and tocopherol) deficiency or excess may yield symptoms of diminishing health such as goitre, scurvy, osteoporosis, weak immune system, disorders of cell metabolism, certain forms of cancer, symptoms of premature aging, and poor psychological health (including eating disorders). The list goes on and on; for reference, see Modern Nutrition in Health and Disease by Shils et al. As of 2005, twelve vitamins and about the same number of minerals are recognized as 'essential nutrients', meaning that they must be consumed and absorbed - or, in the case of vitamin D, alternatively synthesized via UVB radiation - to prevent deficiency symptoms and death. Certain vitamin-like substances found in foods, such as carnitine, have also been found essential to survival and health, but these are not strictly 'essential' to eat because the body can produce them from other compounds. Moreover, thousands of different phytochemicals have recently been discovered in food (particularly in fresh vegetables), which have many discovered and yet to be discovered properties including antioxidant activity (see below). Other essential nutrients include essential amino acids, choline and the essential fatty acids. In addition to sufficient intake, an appropriate balance of essential fatty acids - omega-3 and omega-6 fatty acids - has been discovered to be crucial for maintaining health. Both of these unique "omega" long-chain polyunsaturated fatty acids are substrates for a class of eicosanoids known as prostaglandins. The omega-3 eicosapentaenoic acid (EPA) (which can be made in the body from the omega-3 essential fatty acid alpha-linolenic acid (LNA), or taken in through marine food sources), serves as building block for series 3 prostaglandins (e.g. weakly-inflammation PGE3). The omega-6 dihomo-gamma-linolenic acid (DGLA) serves as building block for series 1 prostaglandins (e.g. anti-inflammatory PGE1), whereas arachidonic acid (AA) serves as building block for series 2 prostaglandins (e.g. pro-inflammatory PGE1). Both DGLA and AA are made from the omega-6 linoleic acid (LA) in the body, or can be taken in directly through food. An appropriately balanced intake of omega-3 and omega-6 partly determines the relative production of different prostaglandins, which partly explains the importance of omega-3/omega-6 balance for cardiovascular health. In industrialised societies, people generally consume large amounts of processed vegetable oils that have reduced amounts of essential fatty acids along with an excessive amount of omega-6 relative to omega-3. The rate of conversions of omega-6 DGLA to AA largely determines the production of the respective prostaglandins PGE1 and PGE2. Omega-3 EPA prevents AA from being released from membranes, thereby skewing prostaglandin balance away from pro-inflammatory PGE2 made from AA toward anti-inflammatory PGE1 made from DGLA. Moreover, the conversion (desaturation) of DGLA to AA is controlled by the enzyme delta-5-desaturase, which in turn is controlled by hormones such as insulin (up-regulation) and glucagon (down-regulation). Because different types and amounts of food eaten/absorbed affect insulin, glucagon and other hormones to varying degrees, not only the amount of omega-3 versus omega-6 eaten but also the general composition of the diet therefore determine health implications in relation to essential fatty acids, inflammation (e.g. immune function) and mitosis (i.e. cell division). Several lines of evidence indicate lifestyle-induced hyperinsulinemia and reduced insulin function (i.e. insulin resistance) as a decisive factor in many disease states. For example, hyperinsulinemia and insulin resistance are strongly linked to chronic inflammation, which in turn is strongly linked to a variety of adverse developments such as arterial microinjuries and clot formation (i.e. heart disease) and exaggerated cell division (i.e. cancer). Hyperinsulinemia and insulin resistance (the so-called metabolic syndrome) are characterized by a combination of abdominal obesity, elevated blood sugar, elevated blood pressure, elevated blood triglycerides, and reduced HDL cholesterol. The negative impact of hyperinsulinemia on prostaglandin PGE1/PGE2 balance may be significant. The state of obesity clearly contributes to insulin resistance, which in turn can cause type 2 diabetes. Virtually all obese and most type 2 diabetic individuals have marked insulin resistance. Although the association between overfatness and insulin resistance is clear, the exact (likely multifarious) causes of insulin resistance remain less clear. Importantly, it has been demonstrated that appropriate exercise, more regular food intake and reducing glycemic load (see below) all can reverse insulin resistance in overfat individuals (and thereby lower blood sugar levels in those who have type 2 diabetes). Overfatness can unfavourably alter hormonal and metabolic status via resistance to the hormone leptin, and a vicious cycle may occur in which insulin/leptin resistance and overfatness aggravate one another. The vicious cycle is putatively fuelled by continuously high insulin/leptin stimulation and fat storage, as a result of high intake of strongly insulin/leptin stimulating foods and energy. Both insulin and leptin normally function as satiety signals to the hypothalamus in the brain; however, insulin/leptin resistance may reduce this signal and therefore allow continued overfeeding despite large bodyfat stores. In addition, reduced leptin signalling to the brain may reduce leptin's normal effect to maintain an appropriately high metabolic rate. There is debate about how and to what extent different dietary factors - e.g. intake of processed carbohydrates, total protein, fat, and carbohydrate intake, intake of saturated and trans fatty acids, and low intake of vitamins/minerals - contribute to the development of insulin- and leptin resistance. In any case, analogous to the way modern man-made pollution may potentially overwhelm the environment's ability to maintain 'homeostasis', the recent explosive introduction of high Glycemic Index- and processed foods into the human diet may potentially overwhelm the body's ability to maintain homeostasis and health (as evidenced by the metabolic syndrome epidemic). Antioxidants are another recent discovery. As cellular metabolism/energy production requires oxygen, potentially damaging (e.g. mutation causing) compounds known as radical oxygen species or free radicals may form. For normal cellular maintenance, growth, and division, these free radicals must be sufficiently neutralized by antioxidant compounds, such as certain vitamins (vitamin C, vitamin E, vitamin K and the aforementioned phytochemicals as well as other compounds, some of which the body itself produces. Different antioxidants are now known to function in a cooperative network, e.g. vitamin C can reactivate free radical-containing glutathione or vitamin E by accepting the free radical itself, and so on. It is now also known that the human digestion system contains a population of a range of bacteria which are essential to digestion, and which are also affected by the food we eat. The role and significance of the intestinal bacterial flora is under investigation.

Nutrition and sports

(Stub, please expand.) Nutrition is very important for improving sports performance. The most common means to improve performance through diet is the practice of eating large quantities of protein, usually red meat, when attempting to build muscle mass; its efficacy is doubtful, as daily protein intake even on a normal diet usually outweighs the amount of muscle protein which can be synthesized in a day, and protein is a much less efficient source of the energy needed to build new muscle tissue than are fats and carbohydrates.

Nutrition and longevity

Lifespan is somehow related to the amount of food energy consumed: this was first systematically investigated in the seminal study by Weidruch, et al. (1986). A pursuit of this principle of caloric restriction followed, involving research into longevity of those who reduced their food energy intake while attempting to optimize their micronutrient intake. Perhaps not surprisingly, some people found that cutting down on food reduced their quality of life so considerably as to negate any possible advantages of lengthening their lives. However, a small set of individuals persists in the lifestyle, going so far as to monitor blood lipid levels and glucose response every few months. See [http://www.calorierestriction.org/ Calorie Restriction Society]. Underlying this research was the hypothesis that oxidative damage was the agent which accelerated aging, and that aging was retarded when the amount of carbohydrates (and thereby insulin release) was reduced through dietary restriction. However, recent research has produced increased longevity in animals (and shows promise for increased human longevity) through the use of insulin uptake retardation. This was done through altering an animal’s metabolism to allow it to consume similar food-energy levels to other animals, but without building up fatty tissue. (Bluher et al, 2003) This has set researchers off on a line of study which presumes that it is not low food energy consumption which increases longevity. Instead, longevity may depend on an efficient fat processing metabolism, and the consequent long term efficient functioning of our organs free from the encumbrance of accumulating fatty deposits. (Das et al, 2004) Thus, longevity may be related to maintained insulin sensitivity. However, several other factors including low body temperature seem to promote longevity also and it is unclear to what extent each of them contribute. Antioxidants have recently come to the forefront of longevity studies which have included the FDA and [http://www.brunswicklabs.com/ Brunswick labs]. In 2005 the FDA issued a statement recommending that Americans should be consuming 7,000 ORAC units daily or 12 full servings of fruit in order to curb the cancer epidemic. The dietary supplement industry has responded by shifting focus away from hormone replacements to “super” antioxidants such as [http://www.proleva.com/ Proleva] which contain whole fruit extracts and ORAC scores near 5,000 units mark or two thirds of the new level set by the FDA.

Nutrition, industry and food processing

Since the Industrial Revolution some two hundred years ago, the food processing industry has invented many technologies that both help keep foods fresh longer and alter the fresh state of food as they appear in nature. Cooling is the primary technology that can help maintain freshness, whereas many more technologies have been invented to allow foods to last longer without becoming spoiled. These latter technologies include pasteurisation, autoclavation, drying, salting, and separation of various components, and all appear to alter the original nutritional contents of food. Pasteurisation and autoclavation (heating techniques) have no doubt improved the safety of many common foods, preventing epidemics of bacterial infection. But some of the (new) food processing technologies undoubtedly have downfalls as well. Modern separation techniques such as milling, centrifugation, and pressing have enabled upconcentration of particular components of food, yielding flour, oils, juices and so on, and even separate fatty acids, amino acids, vitamins, and minerals. Inevitably, such large scale upconcentration changes the nutritional content of food, saving certain nutrients while removing others. Heating techniques may also reduce food's content of many heat-labile nutrients such as certain vitamins and phytochemicals, and possibly other yet to be discovered substances. Because of reduced nutritional value, processed foods are often 'enriched' or 'fortified' with some of the most critical nutrients (usually certain vitamins) that were lost during processing. Nonetheless, processed foods tend to have an inferior nutritional profile than do whole, fresh foods, regarding content of both sugar and high GI starches, potassium/sodium, vitamins, fibre, and of intact, unoxidized (essential) fatty acids. In addition, processed foods often contain potentially harmful substances such as oxidized fats and trans fatty acids. A dramatic example of the effect of food processing on a population's health is the history of epidemics of beri-beri in people subsisting on polished rice. Removing the outer layer of rice by polishing it removes with it the essential vitamin thiamin, causing beri-beri. Another example is the development of scurvy among infants in the late 1800's in the United States. It turned out that the vast majority of sufferers were being fed milk that had been heat-treated (as suggested by Pasteur) to control bacterial disease. Pasteurisation was effective against bacteria, but it destroyed the vitamin C. As mentioned, lifestyle- and obesity-related diseases are becoming increasingly prevalent all around the world. There is little doubt that the increasingly widespread application of some modern food processing technologies has contributed to this development. The food processing industry is a major part of modern economy, and as such it is influential in political decisions (e.g. nutritional recommendations, agricultural subsidising). In any known profit-driven economy, health considerations are hardly a priority; effective production of cheap foods with a long shelf-life is more the trend. In general, whole, fresh foods have a relatively short shelf-life and are less profitable to produce and sell than are more processed foods. Thus the consumer is left with the choice between more expensive but nutritionally superior whole, fresh foods, and cheap, usually nutritionally inferior processed foods. Because processed foods are often cheaper, more convenient (in both purchasing, storage, and preparation), and more available, the consumption of nutritionally inferior foods has been increasing throughout the world along with many nutrition-related health complications.

Policy advice and guidance on nutrition

Most Governments provide guidance on good nutrition, and some also impose mandatory labelling requirements upon processed food manufacturers to assist consumers in complying with such guidance. Current dietary guidelines in the United States are presented in the concept of a food pyramid. There is no apparent consisteny in science-based nutritional recommendations between countries, indicating the role of politics as well as cultural bias in research emphasis and int