Metablism

Metabolism is the complete set of chemical reactions that occur in living cells. These processes are the basis of life, allowing cells to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism yields energy, an example being the breakdown of food in cellular respiration. Anabolism, on the other hand, uses this energy to construct components of cells such as proteins and nucleic acids.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism because they allow cells to drive desirable but thermodynamically unfavorable reactions by coupling them to favorable ones. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell's environment or signals from other cells.

The metabolism of an organism determines which substances it will find nutritious and which it will find poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The speed of metabolism, the metabolic rate, also influences how much food an organism will require.

A striking feature of metabolism is the similarity of the basic metabolic pathways between even vastly different species. For example, the set of chemical intermediates in the citric acid cycle are found universally, among living cells as diverse as the unicellular bacteria Escherichia coli and huge multicellular organisms like elephants.[2] This shared metabolic structure is most likely the result of the high efficiency of these pathways, and of their early appearance in evolutionary history.

Key biochemicals
Structure of a triacylglycerol lipid.Most of the structures that make up animals, plants and microbes are made from three basic classes of molecule: amino acids, carbohydrates and lipids (often called fats). As these molecules are vital for life, metabolism focuses on making these molecules, in the construction of cells and tissues, or breaking them down and using them as a source of energy, in the digestion and use of food. Many important biochemicals can be joined together to make polymers such as DNA and proteins. These macromolecules are essential parts of all living organisms. Some of the most common biological polymers are listed in the table below.

Type of molecule Name of monomer forms Name of polymer forms Examples of polymer forms
Amino acids Amino acids Proteins (also called polypeptides) Fibrous proteins and globular proteins
Carbohydrates Monosaccharides Polysaccharides Starch, glycogen and cellulose
Nucleic acids Nucleotides Polynucleotides DNA and RNA

Amino acids and proteins
Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds. Many proteins are the enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as the proteins in the cytoskeleton that form a system of scaffolding to maintain cell shape. Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes and the cell cycle.

Lipids
Lipids are the most diverse group of biochemicals. Their main structural uses are as part of biological membranes such as the cell membrane, or as a source of energy. Lipids are usually defined as hydrophobic or amphipathic biological molecules that will dissolve in organic solvents such as benzene or chloroform. The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acid esters is a triacylglyceride. Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, and hydrophilic groups such as phosphate in phospholipids. Steroids such as cholesterol are another major class of lipids that are made in cells.

Carbohydrates
Glucose can exist in both a straight-chain and ring form.Carbohydrates are straight-chain aldehydes or ketones with many hydroxyl groups that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals).[6] The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.

Nucleotides
The polymers DNA and RNA are long chains of nucleotides. These molecules are critical for the storage and use of genetic information, through the processes of transcription and protein biosynthesis.[6] This information is protected by DNA repair mechanisms and propagated through DNA replication. A few viruses have an RNA genome, for example HIV, which uses reverse transcription to create a DNA template from its viral RNA genome. RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic group transfer reactions.

Coenzymes
Structure of the coenzyme acetyl-CoA.The transferable acetyl group is bonded to the sulphur atom at the extreme left.Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups. This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are called coenzymes. Each class of group-transfer reaction is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously being made, consumed and then recycled.

The most central coenzyme is adenosine triphosphate (ATP), the universal energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day.[14] ATP acts as a bridge between catabolism and anabolism, with catabolic reactions generating ATP and anabolic reactions consuming it. It also serves as a carrier of phosphate groups in phosphorylation reactions.

A vitamin is an organic compound needed in small quantities that cannot be made in the cells. In human nutrition, most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells. Nicotinamide adenine dinucleotide (NADH), a derivative of vitamin B3 (niacin), is an important coenzyme that acts as a hydrogen acceptor. Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD+ into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates. Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD+/NADH form is more important in catabolic reactions, while NADP+/NADPH is used in anabolic reactions.

Metablism

Lyme Dease

Lyme disease (Borreliosis) is a bacterial infection with a spirochete from the species complex Borrelia burgdorferi, which is most often acquired from the bite of an infected Ixodes, or black-legged, tick, also known as a deer tick. The deer tick is not the only carrier of this disease. The deer tick is frequently mistaken for a dog tick which is more common and larger in size. Borrelia burgdorferi sensu stricto is the predominant cause of Lyme disease in the U.S.; Lyme disease in Europe is more often caused by Borrelia afzelii or Borrelia garinii.

The disease varies widely in its presentation, which may include a rash and flu-like symptoms in its initial stage, followed by the possibility of musculoskeletal, arthritic, neurologic, psychiatric and cardiac manifestations. In most cases of Lyme disease, symptoms can be eliminated with antibiotics, especially if treatment is begun early in the course of illness.

A percentage of patients with Lyme disease have symptoms that last months to years after treatment with antibiotics. These symptoms can include muscle and joint pains, arthritis, stiff neck, cognitive defects, neurological complaints or fatigue. The cause of these continuing symptoms is not yet known. There is some evidence that they may result from an autoimmune type of response, in which a person’s immune system continues to respond even after the infection has been cleared, as well as evidence of ongoing infection with the spirochete.

Delayed or inadequate treatment may often lead to "late stage" Lyme disease that is disabling and difficult to treat. Amid great controversy over diagnosis, testing and treatment, two different standards of care for Lyme disease have emerged.

History
The first record of a condition associated with Lyme disease dates back to 1883 in Breslau, former Germany, where a physician named Alfred Buchwald described a degenerative skin disorder now known as Acrodermatitis Chronica Atrophicans.

In a 1909 meeting of the Swedish Society of Dermatology, Arvid Afzelius presented research about an expanding, ring like lesion he had observed. Afzelius published his work 12 years later and speculated that the rash came from the bite of an Ixodes tick, meningitic symptoms and signs in a number of cases and that both sexes were affected. This rash is now known as erythema migrans (EM), the skin rash found in early stage Lyme disease.

In the 1920s, French physicians Garin and Bujadoux described a patient with meningoencephalitis, painful sensory radiculitis, and erythema migrans following a tick bite, and they postulated the symptoms were due to a spirochetal infection. In the 1940s, German neurologist Alfred Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.

In 1948 spirochete-like structures were observed in skin specimens by Swedish dermatologist Carl Lennhoff. In the 1950s relations between tick bite, lymphocytoma, EM and Bannwarth's syndrome are seen throughout Europe leading to the use of penicillin for treatment.

Interest in tick-borne infections in the U.S. began with the first report of tick-borne relapsing fever (Borrelia hermsii) in 1915, following the recognition of five human patients in Colorado. In 1970 a physician in Wisconsin named Rudolph Scrimenti reports the first case of EM in U.S. and treats it with penicillin based on European literature.

The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns Lyme and Old Lyme, which gave the disease its popular name. This was investigated by Allen Steere, and others from Yale University. The recognition that the patients in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe.

Before 1976, elements of Borrelia burgdorferi sensu lato infection were called or known as Tickborne meningopolyneuritis, Garin-Bujadoux syndrome, Bannworth syndrome, Afzelius syndrome, Montauk Knee or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease, Lyme borreliosis or simply borreliosis.

In 1980 Steere, et al, began to test antibiotic regimens in adult patients with Lyme disease.

In 1982 a novel spirochete was cultured from the mid-gut of Ixodes ticks in Shelter Island, New York, and subsequently from patients with Lyme disease. The infecting agent was then identified by Jorge Benach at the State University of New York at Stony Brook, and soon after isolated by Willy Burgdorfer, a scientist at the National Institutes of Health, who specialized in the study of spirochete microorganisms. The spirochete was named Borrelia burgdorferi in his honor. Burgdorfer was the partner in the successful effort to culture the spirochete, along with Alan Barbour.

After identification of the Lyme disease agent, Borrelia burgdorferi, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics, amoxicillin, cefuroxime axetil, intravenous and intramuscular penicillin and intravenous ceftriaxone.

After the isolation of the spirochete from the mid-gut of Ixodes ticks, how ticks actually transmitted this new pathogen was the subject of much discussion. The hypothesis that Lyme disease spirochetes were transmitted via the salivary gland route of Ixodes ticks was confirmed when spirochetes were actually identified in tick saliva in 1987.

Microbiology
Borrelia bacteria, the causative agent of lyme disease. Magnified 400 times.Lyme disease is caused by spirochetal bacteria from the genus Borrelia, which has at least 37 known species, 12 of which are Lyme related, and an unknown number of genomic strains. The Borrelia species known to cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and have been found to have greater strain diversity than previously estimated.

Until recently it was thought that only three genospecies caused Lyme disease: B. burgdorferi sensu stricto (predominant in North America, but also in Europe), B. afzelii, and B. garinii (both predominant in Eurasia). However, newly discovered genospecies have also been found to cause disease in humans.

Borrelia is a gram negative bacterium.

Transmission

By ticks
Hard-bodied (Ixodes) ticks are the primary Lyme disease vectors. There have also been reports of lyme disease from cats and kittens. In Europe, Ixodes ricinus (known commonly as the sheep tick, castor bean tick, or European castor bean tick) is the transmitter. In North America, Ixodes scapularis (black-legged tick or deer tick) has been identified as the key to the disease's spread on the east coast, while on the west coast the primary vector is Ixodes pacificus (Western black-legged tick). It is important to note that the majority of infections are caused by ticks in the nymph stage, as adult ticks do not become infected through feeding.

Another possible vector is Amblyomma americanum (Lone Star tick), which is found throughout the southeastern U.S. as far west as Texas, and increasingly in northeastern states as well.

It is believed that the longer the duration of tick attachment, the greater the risk of disease transmission; typically, for the spirochete to be transferred, the tick must be attached for a minimum of 24 hours, although only the first part of this statement can be said to be strictly correct.

Unfortunately only about 20% of persons infected with Lyme disease by the deer tick are aware of having had any tick bite, making early detection difficult in the absence of a rash. Tick bites usually go unnoticed due to the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite.

New research suggests that transmission can occur within a few hours of tick attachment, and that the rate of transmission by infected ticks may be much higher than previously assumed.

Congenital
Lyme disease can be transmitted from an infected mother to fetus through the placenta during pregnancy, possibly resulting in stillbirth. The risk of transmission is minimized if the mother receives prompt antibiotic treatment. Antibiotics that can be given to pregnant women with Lyme disease include amoxicillin, cefuroxime axetil, or penicillin (oral or intramuscular).

Other
There is at least one case report of transmission by a biting fly. Lyme spirochetes have been found in biting flies as well as mosquitos. Some researchers believe biting insects do not feed long enough to transmit the infection, while others including Borrelia burgdorferi discoverer Willy Burgdorfer believe more research is needed. Sexual transmission has been anecdotally reported; Lyme spirochetes have been found in semen[34] and breast milk,however sexual transmission of the spirochete by these routes is not known to occur.

Lyme Dease

Hyperthyrodism

Hyperthyroidism (or "overactive thyroid gland") is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both.

Causes
Hyperthyroidism is the result of excess thyroid hormone production, causing an overactive metabolism and increased speed of all the body's processes.

Thyroid hormone generally controls the pace of all of the processes in the body. This pace is called your metabolism. If there is too much thyroid hormone, every function of the body tends to speed up. The thyroid gland regulates the body temperature by secreting two hormones that control how quickly the body burns calories and energy. If the thyroid produces too much hormone, the condition is called hyperthyroidism, but if too little is produced the result is hypothyroidism.

Major causes in humans are:

Graves' disease (the most common etiology with 70-80%)
Toxic thyroid adenoma
Toxic multinodular goitre
AIDS
Other causes of hyperthyroxinemia (high blood levels of thyroid hormones) are not to be confused with true hyperthyroidism and include subacute and other forms of thyroiditis (inflammation) and struma ovarii (a teratoma). Thyrotoxicosis (symptoms caused by hyperthyroxinemia) can occur in both hyperthyroidism and thyroiditis. When it causes acutely increased metabolism, it is sometimes called "thyroid storm", a life-threatening event characterized by tachycardia, hypertension, and fever.

Excess thyroid hormone from pills can also cause hyperthyroidism. Amiodarone, a heart medication, can sometimes cause hyperthyroidism. Hamburger toxicosis is a condition that occurs sporadically and is associated with ground beef contaminated with thyroid hormone.

Postpartum thyroiditis occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. Many times, the hyperthyroidism corrects itself within weeks or months without any treatment necessary.

Signs and symptoms
Major clinical weight loss (often accompanied by a ravenous appetite), intolerance to heat, fatigue, weakness, hyperactivity, irritability, apathy, depression, polyuria, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), shortness of breath (dyspnea), loss of libido, nausea, vomiting, and diarrhea. In the elderly, these classical symptoms may not be present and they may present only with fatigue and weight loss leading to apathetic hyperthyroidism.

Neurological manifestations are tremor, chorea, myopathy, and periodic paralysis. Stroke of cardioembolic origin due to coexisting atrial fibrillation may be mentioned as one of the most serious complications of hyperthyroidism.

As to other autoimmune disorders related with thyrotoxicosis, an association between thyroid disease and myasthenia gravis has been well recognized. The thyroid disease, in this condition, is often an autoimmune one and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is as yet unknown. Some very rare neurological manifestations that are reported to be dubiously associated with thyrotoxicosis are pseudotumor cerebri, amyotrophic lateral sclerosis and a Guillain-Barré-like syndrome.

Minor ocular signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare") and lid-lag. These "fear-like" eye-signs result from thyroid hormone's exacerbation of the action of norepinephrine. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). In lid-lag (von Graefe's sign), when the patient tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism, or treatment by certain anti-adrenergic drugs.

Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball) which occurs in one thyroid-related disease (Graves' disease), but which is not caused by the hyperthyroid state in that disease, and is unrelated to it. Exophthalmos when present may exacerbate these signs, however.

Diagnosis
A diagnosis is suspected through blood tests, by measuring the level of thyroid-stimulating hormone (TSH) in the blood. A low TSH (the job of TSH taken over by thyroid-stimulating immunoglobulin [TSI] that act like TSH) indicates increased levels of T4 and/or T3 in the blood. Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves' disease, may contribute to the diagnosis. In all patients with hyperthyroxinemia, scintigraphy is required in order to distinguish true hyperthyroidism from thyroiditis.

Treatment
The major and generally accepted modalities for treatment of hyperthyroidism in humans involve initial temporary use of suppressive thyrostatics medication, and possibly later use of permanent surgical or radioisotope therapy. All approaches may cause under active thyroid function (hypothyroidism) which is easily managed with levothyroxine supplementation.

Temporary medical therapy

Thyrostatics
Thyrostatics are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in UK) and methimazole (used in US), or where these not tolerated then propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase.

If too high a dose is used in pharmacological treatment, patients can develop symptoms of hypothyroidism.

Beta-blockers
Beta-blockers do not treat, but rather mask, common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety. Propranolol in the UK, and Metoprolol in the US, are most frequently used to augment treatment for hyperthyroid patients.

Permanent treatments
Surgery as an option predates the use of the less invasive radioisotope therapy, but is still required in cases where the thyroid gland is enlarged and causing compression to the neck structures, or the underlying cause of the hyperthyroidism may be cancerous in origin.

Surgery
Surgery (to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method. However, some Graves' disease patients who cannot tolerate medicines for one reason or another or patients who refuse radioiodine opt for surgical intervention. Also, some surgeons believe that radioiodine treatment is unsafe in patients with unusually large gland, or those whose eyes have begun to bulge from their sockets, claiming that the massive dose of iodine needed will only exacerbate the patient's symptoms. The procedure is quite safe - some surgeons even perform partial thyroidectomies on an out-patient basis.

Radioiodine
In Iodine-131 (Radioiodine) Radioisotope Therapy, radioactive iodine is given orally (either by pill or liquid) on a one-time basis to destroy the function of a hyperactive gland. The iodine given for ablative treatment is different from the iodine used in a scan. Radioactive iodine is given after a routine iodine scan, and uptake of the iodine is determined to confirm hyperthyroidism. The radioactive iodine is picked up by the active cells in the thyroid and destroys them. Since iodine is only picked up by thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioactive iodine ablation has been safely used for over 50 years, and the only major reasons for not using it are pregnancy and breast-feeding.

Often, due to the difficulty of picking the correct dose, the treatment results in an opposite condition - hypothyroidism.

Veterinary medicine
In veterinary medicine, hyperthyroidism is one of the most common endocrine conditions affecting older domesticated cats. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. In cats, the cause of hyperthyroidism continues to be researched. Most recently, mutations of the thyroid stimulating hormone receptor have been discovered which cause a constitutive activation of the thyroid gland cells. Many other factors may play a role in the pathogenesis of the disease such as goitrogens (isoflavones such as genistein, daidzein and quercertin) and iodine and selenium content in the diet.

The most common presenting symptoms are: rapid weight loss, tachycardia (rapid heart rate), vomiting, diarrhoea, increased consumption of fluids (polydipsia) and food, and increased urine production (polyuria).

The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). Drugs must be given to cats for the remainder of their lives, but may be the least expensive option, especially for very old cats. Radioiodine treatment and surgery often cure hyperthyroidism. Some veterinarians prefer radioiodine treatment over surgery because it does not carry the risks associated with anesthesia. Radioiodine treatment, however, is not available in all areas for cats. The reason is that this treatment requires nuclear radiological expertise and facilities, since the animal's urine is radioactive for several days after the treatment, requiring special inpatient handling and facilities.

Hyperthyrodism

Bariatric Surger

Gastric bypass procedures (GBP) are any of a group of similar operations used to treat morbid obesity—the severe accumulation of excess weight as fatty tissue—and the health problems (comorbidities) it causes. Bariatric surgery is the term encompassing all of the surgical treatments for morbid obesity, not just gastric bypasses, which make up only one class of such operations.

A gastric bypass first divides the stomach into a small upper pouch and a much larger, lower "remnant" pouch and then re-arranges the small intestine to allow both pouches to stay connected to it. Surgeons have developed several different ways to reconnect the intestine, thus leading to several different GBP names. Any GBP leads to a marked reduction in the functional volume of the stomach, accompanied by an altered physiological and psychological response to food. The resulting weight loss, typically dramatic, markedly reduces comorbidities.

Comorbid conditions
Life-threatening health problems arise from obesity as a consequence of its mechanical or metabolic effects. These comorbidities may in turn lead to severe deterioration of health, shortened life expectancy, and lower quality of life.

Major comorbidities include:
Atherosclerotic cardiovascular disease. Obesity is not only associated with the occurrence of hypercholesterolemia and hypertriglyceridemia, but it is also a factor in the occurrence of atherosclerosis, the deposition of fats within the walls of the blood vessels. This leads to conditions such as coronary artery disease, congestive heart failure, and "hardening of the arteries." This group of conditions is a leading cause of death in the United States.
Diabetes mellitus type 2 occurs mostly in middle and old age, but it is up to 40 times more likely in those who are severely overweight. It is associated with ASCVD, kidney failure, blindness, nerve damage, and amputations of the extremities, and is also a leading overall cause of death in the United States. Dysmetabolic Syndrome X, a pre-diabetic condition often associated with obesity, is accompanied by elevated levels of insulin in the blood and a high incidence of early development of coronary heart disease.
Essential hypertension or "high blood pressure," is much more common in obese individuals. It can lead to early development of ASCVD, as well as to kidney disease. Weight loss is considered to be an important feature of treatment.
Obstructive sleep apnea (OSA) Persons with this condition tend to suffer from airway obstruction when asleep, as the muscles relax and the weight and bulk of tissues collapses the throat passages. An observer notices loud snoring, frequent periods when breathing ceases (apneas), and episodes of restlessness and partial awakening. The afflicted patient is often unaware of the nature of the problem, but may notice frequent awakening at night, dry mouth, a sense of having slept poorly, daytime drowsiness and fatigue, or inappropriate sleeping (such as at work, in meetings, or while driving). This condition has a significant associated mortality.
Gastroesophageal reflux disease (GERD) is characterized by regurgitation (reflux) of acid and gastric contents into the esophagus, and sometimes into the back of the throat. Gastric acid and bile are very corrosive to the lining membrane of the esophagus, and cause it to become inflamed (esophagitis) and sometimes scarred (esophageal stricture). Reflux which occurs while sleeping can lead to sudden coughing and choking at night, a burning sensation in the throat (pyrosis), and inhalation of acid and stomach contents into the lungs, with the risk of hoarseness, bronchitis, pneumonia, lung abscess and lung scarring. GERD is often associated with development of asthma, and causation of asthmatic attacks, and may also be aggravated by OSA.
Gallbladder disease is much more likely in obese individuals, being associated with formation of gallstones, usually composed of crystallized cholesterol, within the gallbladder. Although readily treatable by removal of the gallbladder (cholecystectomy), it may lead to life-threatening problems such as obstruction of the ducts from the liver, jaundice, and inflammation of the pancreas (gallstone pancreatitis).
Liver disease is present in some degree in 90% of persons who undergo bariatric surgery, usually a manifestation of the metabolic effects of obesity on the liver. This may take the form of large fat globules within the liver cells (steatosis), chronic inflammation of the liver (steatohepatitis), and in a few instances, cirrhosis of the liver. The latter condition may lead to liver failure and the need for a liver transplant.
Venous thromboembolic disease affects the legs, and causes swelling, thickening and discoloration of the skin, and ulceration of the skin. This condition begins with damage to the veins of the legs, associated with formation of blood clots (thrombophlebitis), often associated with an injury, a pregnancy (even use of birth-control pills or hormones), or a surgical operation. When a newly formed blood clot breaks loose, and floats through the veins to the heart and lungs, it is called a Pulmonary embolus, which may sometimes be fatal within minutes. More commonly, the blood clot remains in place locally, and heals by becoming a scar, which permanently damages the vein. Once damaged, the veins cannot fully function to return blood to the heart, and increased venous pressure in the legs causes swelling, impaired circulation in the skin, and sometimes skin breakdown. Obesity is a major risk factor in development of VTE, and may also aggravate the increased venous pressure in the legs.
Degenerative disc disease is a progressive "wearing-out" of the cartilaginous disks between the vertebral bones of the spine. It occurs more often and earlier in life in obese persons, due to the markedly increased mechanical stress on the disks from the extra weight. Its most common sign is chronic low back pain, which may be disabling. This condition is also associated with sciatica, lumbar spondylosis, and spinal stenosis.
Degenerative disease of the weight-bearing joints, or osteoarthritis, affecting the hips, knees, ankles and feet, occurs earlier in life, and in greater degree, in obese individuals, due to the mechanical stresses of excess weight. Joint pain, loss of mobility, and joint replacement surgery are much more likely in obese persons.

Surgical indications
Gastric Bypass is indicated for the surgical treatment of morbid obesity, a diagnosis which is made when the patient is seriously obese, has been unable to achieve satisfactory and sustained weight loss by dietary efforts, and is suffering from co-morbid conditions which are either life-threatening or a serious impairment to the quality of life.

In the past, serious obesity was interpreted to mean weighing at least 100 pounds (45 kg) more than the "ideal body weight," an actuarially determined body weight at which one was estimated to be likely to live the longest, as determined by the life insurance industry. This criterion failed for persons of short stature.

In 1991, a Consensus Panel of physicians was sponsored by the National Institutes of Health, and its recommendations have set the current standard for consideration of surgical treatment, the body mass index (BMI). The BMI is defined as the body weight (in kilograms), divided by the square of the height (in meters). The result is expressed as a number usually between 20 and 70, in units of kilograms per square meter.

The Consensus Panel of the National Institutes of Health (NIH) recommended the following criteria for consideration of bariatric surgery, including gastric bypass procedures:

People who have a body mass index (BMI) of 40 or higher. Or,
People with a BMI of 35 or higher with one or more related comorbid conditions.
The Consensus Panel also emphasized the necessity of multidisciplinary care of the bariatric surgical patient, by a team of physicians and therapists, to manage associated co-morbidities, nutrition, physical activity, behavior and psychological needs. The surgical procedure is best regarded as a tool which enables the patient to alter lifestyle and eating habits, and to achieve effective and permanent management of their obesity and eating behavior.

Since 1991, major developments in the field of bariatric surgery, particularly laparoscopy, have outdated some of the conclusions of the NIH panel. In 2004, a Consensus Conference was sponsored by the American Society for Bariatric Surgery (ASBS), which updated the evidence and the conclusions of the NIH panel. This Conference, composed of physicians and scientists of many disciplines, both surgical and non-surgical, reached several conclusions, amongst which were:

Bariatric surgery is the most effective treatment for morbid obesity
Gastric bypass is one of four types of operations for morbid obesity.
Laparoscopic surgery is equally effective and as safe as open surgery.
Patients should undergo comprehensive pre-operative evaluation, and have multi-disciplinary support, for optimum outcome.

Surgical techniques
The gastric bypass, in its various forms, accounts for a large majority of the bariatric surgical procedures performed. It is estimated that 140,000 such operations were performed in the United States in 2005. An increasing number of these operations are now performed by limited access techniques, termed "laparoscopy".

Laparoscopic surgery is performed using several small incisions, or ports, one of which conveys a surgical telescope connected to a video camera, and others permit access of specialized operating instruments. The surgeon actually views his operation on a video screen. The method is also called limited access surgery, reflecting both the limitation on handling and feeling tissues, and also the limited resolution and two-dimensionality of the video image. With experience, a skilled laparoscopic surgeon can perform most procedures as expeditiously as with an open incision — with the option of using an incision should the need arise.

The Laparoscopic Gastric Bypass, Roux-en-Y, first performed in 1993, is regarded as one of the most difficult procedures to perform by limited access techniques, but use of this method has greatly popularized the operation, with benefits which include shortened hospital stay, reduced discomfort, shorter recovery time, less scarring, and minimal risk of incisional hernia.

Essential features
The gastric bypass procedure consists in essence of:

Creation of a small, (15–30 mL/1–2 tbsp) thumb-sized pouch from the upper stomach, accompanied by bypass of the remaining stomach (about 400 mL and variable). This restricts the volume of food which can be eaten. The stomach may simply be partitioned (typically by the use of surgical staples), or it may be totally divided into two parts (also with staplers). Total division is usually advocated, to reduce the possibility that the two parts of the stomach will heal back together ("fistulize"), negating the operation.
Re-construction of the GI tract to enable drainage of both segments of the stomach. The technique of this reconstruction produces several variants of the operation, which differ in the lengths of small bowel used, the degree to which food absorption is affected, and the likelihood of adverse nutritional effects.

Variations of the gastric bypass

Gastric bypass, Roux en-Y (proximal)

Graphic of a Gastric Bypass, Roux en-YThis variant is the most commonly employed gastric bypass technique, and is by far the most commonly performed bariatric procedure in the United States. It is the operation which is least likely to result in nutritional difficulties. The small bowel is divided about 45 cm (18 in) below the lower stomach outlet, and is re-arranged into a Y-configuration, to enable outflow of food from the small upper stomach pouch, via a "Roux limb". In the proximal version, the Y-intersection is formed near the upper (proximal) end of the small bowel. The Roux limb is constructed with a length of 80 to 150 cm (30 to 60 inches), preserving most of the small bowel for absorption of nutrients. The patient experiences very rapid onset of a sense of stomach-fullness, followed by a feeling of growing satiety, or "indifference" to food, shortly after the start of a meal.

Gastric bypass, Roux en-Y (distal)
The normal small bowel is 600 to 1000 cm (20 to 33 feet) in length. As the Y-connection is moved farther down the Gastrointestinal tract, the amount of bowel capable of fully absorbing nutrients is progressively reduced, in pursuit of greater effectiveness of the operation. The Y-connection is formed much closer to the lower (distal) end of the small bowel, usually 100 to 150 cm (40 to 60 inches) from the lower end of the bowel, causing reduced absorption (mal-absorption) of food, primarily of fats and starches, but also of various minerals, and the fat-soluble vitamins. The unabsorbed fats and starches pass into the large intestine, where bacterial actions may act on them to produce irritants and malodorous gases. These increasing nutritional effects are traded for a relatively modest increase in total weight loss.

Loop Gastric bypass ("Mini-gastric bypass")
The first use of the gastric bypass, in 1967, used a loop of small bowel for re-construction, rather than a Y-construction as is prevalent today. Although simpler to create, this approach allowed bile and pancreatic enzymes from the small bowel to enter the esophagus, sometimes causing severe inflammation and ulceration of either the stomach or the lower esophagus. If a leak into the abdomen occurs, this corrosive fluid can cause severe consequences. Numerous studies show the loop reconstruction (Billroth II gastrojejunostomy) works more safely when placed low on the stomach, but can be a disaster when placed adjacent to the esophagus. Thus even today thousands of "loops" are used for general surgical procedures such as ulcer surgery, stomach cancer and injury to the stomach, but bariatric surgeons abandoned use of the construction in the 1970s, when it was recognized that its risk is not justified for weight management.

The Mini-Gastric Bypass, which uses the loop reconstruction, has been suggested as an alternative to the Roux en-Y procedure, due to the simplicity of its construction, which reduced the challenge of laparascopic surgery. It is claimed that construction of a long tubular gastric pouch reduces the risk of inflammatory complications, and renders it as safe as the RNY technique. Most bariatric surgeons shun the procedure, and most would assert that it remains unproven and investigational in nature at this time.

Physiology of the gastric bypass
The gastric bypass reduces the size of the stomach by well over 90%. A normal stomach can stretch, sometimes to over 1000 ml, while the pouch of the gastric bypass may be 15 ml in size. The Gastric Bypass pouch is usually formed from the part of the stomach which is least susceptible to stretching. That, and its small original size, prevents any significant long-term change in pouch volume. What does change, over time, is the size of the connection between stomach and bowel, and the ability of the small bowel to hold a greater volume of food. Over time, the functional capacity of the pouch increases; by that time, weight loss has occurred, and the increased capacity serves to allow maintenance of a lower body weight.

When the patient ingests just a small amount of food, the first response is a stretching of the wall of the stomach pouch, stimulating nerves which tell the brain that the stomach is full. The patient feels a sensation of fullness, as if they had just eaten a large meal — but with just a thumbful of food. Most people do not stop eating simply in response to a feeling of fullness, but the patient rapidly learns that subsequent bites must be eaten very slowly and carefully, to avoid increasing discomfort, or even vomiting.

Normally when we eat, food passes out of the stomach into the duodenum after about 30 minutes. When it reaches the lower end of the duodenum, a new hormonal message is generated, telling the brain that enough food has been eaten. The person with a normal GI tract experiences this hormone release as a sense of satisfaction or "satiety" — a feeling of indifference toward eating any more. Recently, a hormone called ghrelin has been discovered, which may contribute to this effect.

To gain the maximum benefit from this physiology, it is important that the patient eat only at mealtimes, 2 to 3 meals daily, and avoid snacks and grazing between meals, which can effectively "bypass the bypass". This requires a change in eating behavior, and alteration of long-acquired habits for finding food. In almost every case where weight gain occurs late after surgery, capacity for a meal has not greatly increased. The cause of regaining weight is eating between meals, usually high-caloric snack foods. There is no known operation which can completely counteract the adverse effects of destructive eating behavior.

Complications
Any major surgery involves the potential for complications — adverse events which increase risk, hospital stay, and mortality. Some complications are common to all abdominal operations, while some are specific to bariatric surgery. A person who chooses to undergo bariatric surgery should know about these risks.


Mortality & Complication Rates
A recent large multi-center study[citation needed] reported that, in experienced hands, the overall complication rate of this type of surgery ranges from 7% for laparoscopic procedures to 14.5% for operations through open incisions, during the 30 days following surgery. Mortality for this study was 0% in 401 laparoscopic cases, and 0.6% in 955 open procedures. Similar mortality rates – 30-day mortality of 0.11%, and 90-day mortality of 0.3% – have been recorded in the U.S. Centers of Excellence program, the results from 33,117 operations at 106 centers.

Mortality is affected by complications, which in turn are affected by pre-existing risk factors such as degree of obesity, heart disease, obstructive sleep apnea, diabetes mellitus, and history of prior pulmonary embolism. It is also affected by the experience of the operating surgeon: the "learning curve" for laparoscopic bariatric surgery is estimated to be about 100 cases, and inexperienced surgeons have been shown in several studies [citation needed] to have a significantly higher rate of complications and mortality. Unfortunately, the way a surgeon becomes experienced in dealing with problems is by enncountering those problems over time.

Complications of abdominal surgery

Infection
Infection of the incisions, or of the inside of the abdomen (peritonitis, abscess) may occur, due to release of bacteria from the bowel during the operation. Nosocomial infection, such as pneumonia, bladder or kidney infections, and sepsis (bloodborne infection) are also possible. Effective short-term use of antibiotics, diligent respiratory therapy, and encouragement of activity within a few hours after surgery, can reduce the risks of infections.

Hemorrhage
Many blood vessels must be cut, to divide the stomach and to move the bowel. Any of these may later begin bleeding, either into the abdomen (intra-abdominal hemorrhage), or into the bowel itself (gastrointestinal hemorrhage). Transfusions may be needed, and re-operation is sometimes necessary. Use of blood thinners, to prevent venous thromboembolic disease, may actually increase the risk of hemorrhage slightly.

Hernia
A hernia is an abnormal opening, either within the abdomen, or through the abdominal wall muscles. An internal hernia may result from surgery, and re-arrangement of the bowel, and is mainly significant as a cause of bowel obstruction. An incisional hernia occurs when a surgical incision does not heal well; the muscles of the abdomen separate and allow protrusion of a sac-like membrane, which may contain bowel or other abdominal contents, and which can be painful and unsightly. The risk of abdominal wall hernia is markedly decreased in laparoscopic surgery.

Bowel obstruction
Abdominal surgery always results in some scarring of the bowel, called adhesions. A hernia, either internal or through the abdominal wall, may also result. When bowel becomes trapped by adhesions or a hernia, it may become kinked and obstructed, sometimes many years after the original procedure. Usually an operation is necessary, to correct this problem.

Venous thromboembolism
Any injury, such as a surgical operation, causes the body to increase the coagulation of the blood. Simultaneously, activity may be reduced. There is an increased probability of formation of clots in the veins of the legs, or sometimes the pelvis, particularly in the morbidly obese patient. A clot which breaks free and floats to the lungs is called a pulmonary embolus, a very dangerous occurrence. Commonly, blood thinners are administered before surgery, to reduce the probability of this type of complication.

Complications of gastric bypass

Anastamotic leakage
An anastamosis is a surgical connection, between the stomach and bowel, or between two parts of the bowel. The surgeon attempts to create a water-tight connection, by connecting the two organs with either staples or sutures, either of which actually makes a hole in the bowel wall. The surgeon will rely on the healing power of the body, and its ability to create a seal like a self-sealing tire, to succeed with the surgery. If that seal fails to form, for any reason, fluid from within the gastrointestinal tract can leak into the sterile abdominal cavity, and give rise to infection and abscess formation. Leakage of an anastamosis can occur in about 2% of gastric bypass procedures, usually at the stomach-bowel connection. Sometimes leakage can be treated with antibiotics, and sometimes it will require immediate re-operation. It is usually safer to re-operate, if an infection cannot be definitely controlled immediately.

Anastamotic stricture
As the anastamosis heals, it forms scar tissue, which naturally tends to shrink ("contract") over time, making the opening smaller. This is called a "stricture". Usually, the passage of food through an anastamosis will keep it stretched open, but if the inflammation and healing process outpaces the stretching process, scarring may make the opening so small that even liquids can no longer pass through it. The solution is a procedure called gastroendoscopy, and stretching of the connection by inflating a balloon inside it. Sometimes this manipulation may have to be performed more than once, to achieve lasting correction.


Dumping syndrome
Normally, the pyloric valve at the lower end of the stomach regulates the release of food into the bowel. When the Gastric Bypass patient eats a sugary food, the sugar passes rapidly into the bowel, where it gives rise to a physiological reaction called dumping syndrome. An affected person feels his heart beating rapidly and forcefully, breaks into a cold sweat, gets a feeling of butterflies in the stomach, and has a "sky is falling" type of anxiety. He usually has to lie down, and is very uncomfortable for about 30 to 45 minutes. Diarrhea may then follow. The dumping syndrome is a response to a behavior which the patient should not be doing anyway: eating sugary foods. It is not life-threatening, and may assist one in making healthier food choices.

Nutritional deficiencies
Hypoparathyroidism, due to inadequate absorption of calcium, may occur in over 30% [citation needed] of GBP patients. Calcium is primarily absorbed in the duodenum, which is bypassed by the surgery. Most patients can achieve adequate calcium absorption by supplementation with Vitamin D and Calcium Citrate (carbonate may not be absorbed - it requires an acidic stomach, which is bypassed).
Iron frequently is seriously deficient, particularly in menstruating females, and must be supplemented. Again, it is normally absorbed in the duodenum. Ferrous sulfate can cause considerable GI distress in normal doses; alternatives include Ferrous fumarate, or a chelated form of iron. Occasionally, a female patient develops severe anemia, even with supplements, and must be treated with parenteral iron.
Vitamin B-12 requires intrinsic factor from the gastric mucosa to be absorbed. In patients with a small gastric pouch, it may not be absorbed, even if supplemented orally, and deficiencies can result in pernicious anemia and neuropathies. Sub-lingual B-12 appears to be adequately absorbed.
Thiamine deficiency (also known as beriberi) will, rarely, occur as the result of its absorption site in the jejunum being bypassed. This deficiency can also result from inadequate nutritional supplements being taken post operatively.
Protein malnutrition is a real risk. Some patients suffer troublesome vomiting after surgery, until their GI tract adjusts to the changes, and cannot eat adequate amounts even with 6 meals a day. Many patients require protein supplementation during the early phases of rapid weight loss, to prevent excessive loss of muscle mass.

Nutritional effects
After surgery, patients feel fullness after ingesting only a small volume of food, followed soon thereafter by a sense of satiety and loss of appetite. Total food intake is markedly reduced. Due to the reduced size of the newly created stomach pouch, and reduced food intake, adequate nutrition demands that the patient follow the surgeon's instructions for food consumption, including the number of meals to be taken daily, adequate protein intake, and the use of vitamin and mineral supplements.

Protein nutrition
Proteins are essential food substances, contained in foods such as meat, fish and poultry, dairy products, soy, and eggs. With reduced ability to eat a large volume of food, gastric bypass patients must focus on eating their protein requirements first, and with each meal. Proximal GBP rarely leads to protein deficiency[citation needed] if this simple precaution is followed. Distal GBP is more likely to lead to protein deficiency, particularly if fat intake is excessive, and the position of the Y-connection is farther downstream.[citation needed] In some cases, surgeons may recommend use of a liquid protein supplement.

Calorie nutrition
The profound weight loss which occurs after bariatric surgery is due to taking in much less energy (calories) than the body needs to use every day. Fat tissue must be burned, to offset the deficit, and weight loss results. Eventually, as the body becomes smaller, its energy requirements are decreased, while the patient simultaneously finds it possible to eat somewhat more food. When the energy consumed is equal to the calories eaten, weight loss will stop. Proximal GBP typically results in loss of 60 to 80% of excess body weight, and very rarely leads to excessive weight loss. The risk of excessive weight loss is slightly greater with Distal GBP.

Vitamins
Vitamins are normally contained in the foods we eat, as well as any supplements we may choose to take. The amount of food which will be eaten after GBP is severely reduced, and vitamin content is correspondingly reduced. Supplements should therefore be taken, to completely cover minimum daily requirements of all vitamins and minerals. Absorption of most vitamins is not seriously affected, after Proximal GBP, although Vitamin B-12 may not be well-absorbed in some persons. Sub-lingual preparations of B-12 will provide adequate absorption. After the Distal GBP, fat-soluble vitamins A, D and E may not be well-absorbed, particularly if fat intake is large. Water-dispersed forms of these vitamins may be indicated, on specific physician recommendation.

Minerals
All versions of the GBP bypass the duodenum, which is the primary site of absorption of both Iron and Calcium. Iron replacement is essential in menstruating females, and supplementation of iron and calcium is preferable in all patients. Ferrous sulfate is poorly tolerated. Alternative forms of iron (fumarate, gluconate, chelates) are less irritating and probably better absorbed. Calcium carbonate preparations should also be avoided; calcium as citrate or gluconate, 1200 mg as calcium, has greater bioavailability independent of acid in the stomach, and will likely be better absorbed.


Results and health Benefits of gastric bypass
Weight loss of 65 to 80% of excess body weight (the amount by which actual body weight exceeds actuarial ideal body weight) is typical of most large series of Gastric Bypass operations reported. The medically more significant effects are a dramatic reduction in co-morbid conditions:

Hyperlipidemia is corrected in over 70% of patients.
Essential hypertension is relieved in over 70% of patients, and medication requirements are usually reduced in the remainder.
Obstructive sleep apnea is markedly improved with weight loss, so that most patients are asymptomatic, and often do not even snore, within one year.
Diabetes mellitus type 2 is reversed in up to 90% of patients, usually leading to a normal blood sugar without medication, sometimes within days of surgery.
Gastroesophageal reflux disease is relieved from the time of surgery in almost all patients.
Venous thromboembolic disease signs such as leg swelling are typically much improved.
Low back pain and joint pain are typically relieved or improved in nearly all patients.
A recent study in a large comparative series of patients showed a 89% reduction in mortality over the 5 years following surgery, compared to a non-surgically treated group of patients. There were accompanying decreases in the incidence of cardiovascular disease, infections, and cancer.

Concurrently, most patients are able to alter their lifestyle, to consume "healthier" foods, exercise more regularly, and to enjoy greater participation in family and social activities. Bariatric surgery is the most effective treatment for morbid obesity, and can markedly improve health and lifestyle.

Living with gastric bypass
Gastric bypass surgery has an emotional, as well as a physiological, impact on the individual. Many who have undergone the surgery suffer from depression in the following months.[1] This is a result of a change in the role food plays in their emotional well-being. Many morbidly obese people use food as an emotional crutch, and the strict limitations on the diet can place great emotional strain on the patient. Energy levels in the period following the surgery will be low. This is due again to the restiction of food intake, but the negative change in emotional state will also have an impact here.[2] It may take as long as three months for emotional levels to rebound. Muscular weakness in the months following surgery is common. This is caused by a number of factors, including a restriction on protein intake, a resulting loss in muscle mass and decline in energy levels. The weakness may result in balance problems, difficulty climbing stairs or lifting heavy objects, and increased fatigue following simple physical tasks. Many of these issues will pass over time as food intake gradually increases. However, the first months following the surgery can be very difficult, an issue not often mentioned by physicians suggesting the surgery. The benefits and risks of this surgery are well established; however, the psychological effects are not well understood, and potential patients should ensure a strong support system before agreeing to the procedure.

Centers of excellence
Persons who are considering bariatric surgery should find an experienced and well-qualified surgeon at a well-equipped hospital, which has a network of collaborating healthcare professionals to assist them in the complete care of the patient's medical, nutritional, and psychological needs. There are two national certification programs which evaluate bariatric surgery centers for:

Surgeon experience
Hospital facilities
Multidisciplinary care available
Complication and mortality rates
Long term follow-up program

SRC Centers of Excellence
The American Society for Bariatric Surgery established the independent Surgical Review Corporation to certify Centers of Excellence. Over 100 qualified bariatric programs, with over 250 surgeons, have been qualified nationwide.

ACS Bariatric Surgery Center Network
The American College of Surgeons Bariatric Surgery Center Network is a listing of centers approved by that organization.

International Federation for the Surgery of Obesity
This multinational organization unites bariatric surgeons of many countries. Many leading American surgeons are also members of the American Society for Bariatric Surgery (ASBS). Persons seeking a qualified surgeon may check the ASBS website, or a listing of IFSO Councils by country.

Bariatric Surger

Early Signs of Dwarfism

Dwarfism refers to a condition of extreme small size of a person, animal, or plant. Any type of marked human smallness could be termed dwarfism in older popular and medical usage. Currently, in both general and technical usage, the term as related to human beings (the major subject of this article) is restricted to those forms of extreme shortness characterized by disproportion of body parts, typically due to an inheritable disorder in bone or cartilage development.

In contrast, those forms of shortness characterized by proportional body parts usually have a hormonal or nutritional cause. An example is growth hormone deficiency, which was once called "Pituitary dwarfism". According to current usage, proportional shortness, even when severe, is no longer referred to as "dwarfism".

Types of dwarfism
Types of dwarfism are often clinically distinguished by the predominant segment of the limbs that is short:

rhizomelic = root, e.g. bones of upper arm or thigh
mesomelic = middle, e.g. bones of forearm or lower leg
acromelic = end, e.g. bones of hands and feet.
When the cause of dwarfism is understood, it may be classified according to one of hundreds of names, which are usually permutations of the following roots:

chondro = of cartilage
osteo = of bone
spondylo = of the vertebrae
plasia = form
trophy = growth
Examples include achondroplasia, osseous dysplasia, chondrodystrophy, and osteochondrodystrophy.

The most recognizable and most common form of dwarfism is achondroplasia, which produces rhizomelic short limbs, increased spinal curvature, and distortion of skull growth. It accounts for 70% of dwarfism cases. Other relatively common types include spondyloepiphyseal dysplasia congenita (SED), diastrophic dysplasia, pseudoachondroplasia, hypochondroplasia, and osteogenesis imperfecta (OI). Severe shortness with skeletal distortion also occurs in several of the mucopolysaccharidoses and other storage diseases.

The average adult height of male and female dwarfism sufferers are 132cm and 123cm respectively.

Genetics
Dwarfism is an autosomal dominant genetic disease effecting a single gene. The allele D is dominant for dwarfism over allele d for normal whereby:

dd = Normal
Dd = Dwarf
DD = Lethal
Those with DD will therefore die in the womb. Unusually for an autosomal dominant disease, 86% of dwarfs have normal parents and acquire the disease due to a de novo mutation, in the same base pair, in the gene encoding fibroblast growth factor receptor 3. This reduces the effect of growth hormones on fibroblasts and, therefore, cartilage growth is severely reduced, giving the characteristic disproportional size of limbs, particularly at proximal sites, for those suffering from dwarfism.

IQ and life expectancy are not effected by this condition and dwarfs are fertile.

Diagnosis
Unusually short stature for a child's age is usually what brings the child to medical attention. Skeletal dysplasia ("dwarfism") is usually suspected because of obvious physical features (e.g., unusual configuration of face or shape of skull), because of an obviously affected parent, or because body measurements (arm span, upper to lower segment ratio) indicate disproportion. Bone x-rays are often the key to diagnosis of a specific skeletal dysplasia, but they are not the key diagnosis. Most children with suspected skeletal dysplasias will be referred to a genetics clinic for diagnostic confirmation and genetic counselling. (See External links, below, for a list of American referral centers with special expertise in skeletal dysplasias.) In the last decade, genetic tests for some of the specific disorders have become available.

During the initial medical evaluation for shortness, the absence of disproportion and the other clues above usually indicates other causes than bone dysplasias. Extreme shortness with completely normal proportions sometimes indicates growth hormone deficiency (pituitary dwarfism).

Short stature alone, in the absence of any other abnormalities, may simply be genetic, particularly if a person is born into a family of people who are relatively short.


Problems associated with dwarfism
The principal adverse effects of dwarfism can be divided into the physical and the social.

Physical effects of malformed bones vary according to the specific disease. Many involve pain resulting from joint damage from abnormal bone alignment, or from nerve compression (e.g, spinal stenosis). Early degenerative joint disease, exaggerated lordosis or scoliosis, and constriction of spinal cord or nerve roots can cause pain and disability. Reduced thoracic size can restrict lung growth and reduce pulmonary function. Some forms of dwarfism are associated with disordered function of other organs, such as the brain or liver, sometimes severely enough to be more disabling than the abnormal bone growth.

The psychosocial disadvantages may be more distressing than the physical symptoms, especially in childhood and adolescence, but people with dwarfism vary greatly in the degree to which social participation and emotional health are affected.

Social prejudice against extreme shortness may reduce social and marital opportunities.
Numerous studies have demonstrated reduced employment opportunities. Severe shortness is associated with lower income.
Self-esteem may be reduced and family relationships affected
Extreme shortness (in the low 2–3 foot [60–90 cm] range) can interfere with ordinary activities of daily living, like driving or even using countertops built for taller people.

Treatment and support
As the genetic defects of most forms of dwarfism due to bone dysplasia cannot be corrected, therapeutic interventions are typically aimed at (1) preventing or reducing pain or physical disability, (2) increasing adult height, or (3) mitigating psychosocial stresses and enhancing social adaptation.

Pain and disability may be ameliorated by physical therapy, by braces or other orthotic devices, or by surgical procedures.

The only simple interventions that increase perceived adult height are dress enhancements such as shoe lifts or hairstyle. Growth hormone is rarely used for shortness due to bone dysplasias, as the height benefit is typically small (less than 5 cm) and the cost high. The most effective means of increasing adult height by several inches is limb-lengthening surgery, though availability is limited and cost is high in terms of dollars, discomfort, and interruption of life. Most people with dwarfism do not avail themselves of this, and it remains controversial. For other types of dwarfism, surgical treatment is not possible.

Early Signs of Dwarfism

Cushings Desease

Cushing's syndrome (also called hypercortisolism or hyperadrenocorticism) is an endocrine disorder caused by high levels of cortisol in the blood from a variety of causes, including primary pituitary adenoma (known as Cushing's disease), primary adrenal hyperplasia or neoplasia, ectopic ACTH production (e.g., from a small cell lung cancer), and iatrogenic (steroid use). Normally, cortisol is released from the adrenal gland in response to ACTH being released from the pituitary gland. Both Cushing's syndrome and Cushing's disease are characterized by elevated levels of cortisol in the blood, but the cause of elevated cortisol differs between the two. Cushing's disease specifically refers to a tumor in the pituitary gland that stimulates excessive release of cortisol from the adrenal gland by releasing large amounts of ACTH. In Cushing's syndrome, ACTH levels will normally drop due to negative feedback from the high levels of cortisol. Cushing's disease was discovered by American physician, surgeon and endocrinologist Harvey Cushing (1869-1939) and reported by him in 1932.

Cushing's syndrome--which is also a relatively common condition in domestic dogs and horses--is characterised by abnormal fat deposition. (The syndrome in horses leads to weight loss, polyuria and polydipsia and may cause laminitis.)

Signs and symptoms
Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), a round face often referred to as a "moon face", excess sweating, telangiectasia (dilation of capillaries), thinning of the skin (which causes easy bruising) and other mucous membranes, purple or red striae (also caused by thinning of the skin) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). A common sign is the growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump). The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety, including panic attacks, are common.

Other signs include persistent hypertension (due to the aldosterone-like effects) and insulin resistance, leading to hyperglycemia (high blood sugars) which can lead to diabetes mellitus. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation of the skin, due to its ability to stimulate melanocyte receptors.

Diagnosis
When Cushing's is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offer equal detection rates (Raff & Findling 2003). Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, high cortisol would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (eg: adrenal adenoma) that is not inhibited by the dexamethasone. A low cortisol reading would be indicative of Cushing's disease because the dexamethasone inhibited the pituitary adenoma so that its' output of ACTH decreased, resulting in decreased cortisol levels. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm causing typical bitemporal hemianopia.

When any of these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the cortisol levels in various veins in the body by venous catheterisation, working towards the pituitary (petrosal sinus sampling) is necessary.

Pathophysiology
Both the hypothalamus and the pituitary gland are in the brain. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release corticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on the pituitary, which decreases the amount of ACTH released from the pituitary gland. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. One of the most common causes of Cushings syndrome is a cortisol secreting adenoma in the cortex of the adrenal gland. The adenoma causes cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low. Cushing's disease refers only to hypercortisolism secondary to excess production of ACTH from a pituitary gland adenoma. This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because a tumor causes the pituitary to be unresponsive to negative feedback from high cortisol levels.

Treatment
If an adrenal adenoma is identified it may be removed by surgery. Pituitary ACTH producing adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed replacement with hydrocortisone or prednisolone is imperative.

In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome (Nelson et al 1960).

Epidemiology
Iatrogenic Cushing's (caused by treatment with corticosteroids) is the most common form of Cushing's syndrome. The incidence of pituitary tumors may be relatively high, as much as one in five people. (Cancer. 2004 Aug 1;101(3):613-9.)

Hyperadrenocorticism in companion animals
Hyperadrenocorticism is a common endocrinopathy in domestic companion animals. Most cases are caused by hyperplasia of the adrenal cortex in response to pituitary dysfunction. Hyperadrenocorticism in companion animals is usually treated with long term drug therapy. In dogs, treatment is accomplished with trilostane or with mitotane. Dogs with pituitary-dependent Cushing's syndrome may be treated by radiation therapy directed against a pituitary adenoma. Dogs productive adrenal tumors may be treated by adrenalectomy.

In Equine Cushings, surgical treatment is impractical, and the drugs pergolide and cyproheptadine are indicated. Pergolide is the treatment of choice, but in view of the high incidence of side effects and the high cost of the drug, cyproheptadine may be used instead.

Canine and Feline Cushing's resources
CanineCushings-AutoimmuneCare
Educational support group for owners of dogs and cats with hyperadrenocorticism. Latest information regarding the diagnosis, treatment (conventional/complementary), and long-term management of Cushing's syndrome (Typical, Atypical, Iatrogenic and Pseudo-Cushing’s Disease).
Cushing Hunde
German-speaking support group for owners of dogs with Cushing's syndrome. Very informative. Sister group to CanineCushings-AutoimmuneCare.
Cushing's Syndrome/Disease in dogs
Equine Cushing's and Insulin Resistance
Equine Metabolic Syndrome
Ferret Health List
Insulinoma Adrenal Ferrets
Canine Cushing’s Syndrome: Diagnosis and Treatment

Cushings Desease

Alchol Calories

Alcohol and weight is a subject relevant to millions of people who like to drink alcoholic beverages and who also either want to maintain or to lose body weight. It is uncertain whether alcohol leads to increase in body weight or if it does not. Some studies find an increase in body weight, some studies do not, and some find a small decrease among women who begin consuming alcohol (Colditz et al.; Hellerstedt et al.; Istvan et al.; Jequer; Kahn et al.; Klesges et al.; Landes; Liu et al.; Mannisto et al., 1996; Mannisto et al., 1997; Prentice; Arif & Rohrer, 2005). Some of these studies are very large; one involved nearly 80,000 and another included 140,000 subjects.

These findings are inconclusive because alcohol itself contains 7 calories per gram, and most alcoholic drinks also contain carbohydrates. The reason that alcohol may not increase weight is unclear, but research suggests that alcohol energy is not efficiently used. Alcohol also appears to increase metabolic rate significantly, thus causing more calories to be burned rather than stored in the body as fat (Klesges et al., 1994). Other research has found consumption of sugar to decrease as consumption of alcohol increases.
The research results do not necessarily mean that people who wish to lose weight should continue to consume alcohol because consumption is known to have an enhancing effect on appetite. The relationship between alcohol and weight remains unresolved and will remain so until more research is conducted that can clarify any apparent discrepancies in findings.

Alchol Calories